Trial Outcomes & Findings for A Study to Evaluate the Pharmacokinetics of PEP005 (Ingenol Mebutate) Gel, 0.05%, When Applied in a Maximal Use Setting to the Dorsal Aspect of the Forearm in Patients With Actinic Keratosis (NCT NCT00852137)
NCT ID: NCT00852137
Last Updated: 2015-03-06
Results Overview
Maximum observed concentration (Cmax) for ingenol mebutate and its two acyl isomers (PEP015 and PEP025) levels over the 24 hour sampling time period based on actual values measured. Blood samples were taken: at 30 minutes, 1, 2, 4, 8, 12 and 24 hours following study medication application on Day 2.
COMPLETED
PHASE2
16 participants
1 day
2015-03-06
Participant Flow
Study Period: First patient randomized: March 18, 2009 Last patient completed Day 57: May 27, 2009 A single site in the US
Participant milestones
| Measure |
PEP005 Gel, 0.05%
PEP005 (ingenol mebutate) Gel 0.05% once daily for 2 consecutive days
|
Vehicle
Vehicle gel once daily for 2 consecutive days
|
|---|---|---|
|
Overall Study
STARTED
|
13
|
3
|
|
Overall Study
COMPLETED
|
13
|
3
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
A Study to Evaluate the Pharmacokinetics of PEP005 (Ingenol Mebutate) Gel, 0.05%, When Applied in a Maximal Use Setting to the Dorsal Aspect of the Forearm in Patients With Actinic Keratosis
Baseline characteristics by cohort
| Measure |
PEP005 Gel, 0.05%
n=13 Participants
PEP005 (ingenol mebutate) Gel 0.05% once daily for 2 consecutive days
|
Vehicle
n=3 Participants
Vehicle gel once daily for 2 consecutive days
|
Total
n=16 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
8 Participants
n=99 Participants
|
2 Participants
n=107 Participants
|
10 Participants
n=206 Participants
|
|
Age, Categorical
>=65 years
|
5 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
6 Participants
n=206 Participants
|
|
Age, Continuous
|
63 years
STANDARD_DEVIATION 9.7 • n=99 Participants
|
64.7 years
STANDARD_DEVIATION 12 • n=107 Participants
|
63.3 years
STANDARD_DEVIATION 9.7 • n=206 Participants
|
|
Sex: Female, Male
Female
|
7 Participants
n=99 Participants
|
3 Participants
n=107 Participants
|
10 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
6 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
6 Participants
n=206 Participants
|
|
Region of Enrollment
United States
|
13 participants
n=99 Participants
|
3 participants
n=107 Participants
|
16 participants
n=206 Participants
|
PRIMARY outcome
Timeframe: 1 dayMaximum observed concentration (Cmax) for ingenol mebutate and its two acyl isomers (PEP015 and PEP025) levels over the 24 hour sampling time period based on actual values measured. Blood samples were taken: at 30 minutes, 1, 2, 4, 8, 12 and 24 hours following study medication application on Day 2.
Outcome measures
| Measure |
PEP005 Gel, 0.05%
n=13 Participants
PEP005 (ingenol mebutate) Gel 0.05% once daily for 2 consecutive days
|
Vehicle
n=3 Participants
Vehicle gel once daily for 2 consecutive days
|
|---|---|---|
|
Maximum Observed Concentration (Cmax) for Ingenol Mebutate and Its Two Acyl Isomers (PEP015 and PEP025) Levels
|
NA ng/mL
Standard Deviation NA
The assay results completed for the interim analysis, confirmed that there were no detectable levels of ingenol mebutate or its acyl isomers (PEP015 or PEP025) in any samples assayed.
|
NA ng/mL
Standard Deviation NA
The assay results completed for the interim analysis, confirmed that there were no detectable levels of ingenol mebutate or its acyl isomers (PEP015 or PEP025) in any samples assayed.
|
PRIMARY outcome
Timeframe: 1 dayTime at which Cmax is attained (Tmax) for ingenol mebutate, and its two acyl isomers (PEP015 and PEP025) levels measured at 30 min, 1, 2, 4, 8, 12 and 24 hours following study medication application on Day 2. If a maximum value occured at more than one timepoint Tmax is defined as the first timepoint with this value.
Outcome measures
| Measure |
PEP005 Gel, 0.05%
n=13 Participants
PEP005 (ingenol mebutate) Gel 0.05% once daily for 2 consecutive days
|
Vehicle
n=3 Participants
Vehicle gel once daily for 2 consecutive days
|
|---|---|---|
|
Time at Which Cmax is Attained (Tmax) for Ingenol Mebutate, and Its Two Acyl Isomers (PEP015 and PEP025) Levels.
|
NA hours
NA
The assay results completed for the interim analysis, confirmed that there were no detectable levels of ingenol mebutate or its acyl isomers (PEP015 or PEP025) in any samples assayed.
|
NA hours
NA
The assay results completed for the interim analysis, confirmed that there were no detectable levels of ingenol mebutate or its acyl isomers (PEP015 or PEP025) in any samples assayed.
|
PRIMARY outcome
Timeframe: 1 dayArea under the blood conc. versus time curve was calculated for time 0-24 hours (AUC(0-24)) for ingenol mebutate and its two acyl isomers (PEP015 and PEP025) levels measured at 30 min, 1, 2, 4, 8, 12 and 24 hours following study medication application on Day 2.
Outcome measures
| Measure |
PEP005 Gel, 0.05%
n=13 Participants
PEP005 (ingenol mebutate) Gel 0.05% once daily for 2 consecutive days
|
Vehicle
n=3 Participants
Vehicle gel once daily for 2 consecutive days
|
|---|---|---|
|
Area Under the Blood Conc. Versus Time Curve for Time 0-24 Hours (AUC(0-24)) for Ingenol Mebutate and Its Two Acyl Isomers (PEP015 and PEP025) Levels
|
NA ng/mL x h
Standard Deviation NA
The assay results completed for the interim analysis, confirmed that there were no detectable levels of ingenol mebutate or its acyl isomers (PEP015 or PEP025) in any samples assayed.
|
NA ng/mL x h
Standard Deviation NA
The assay results completed for the interim analysis, confirmed that there were no detectable levels of ingenol mebutate or its acyl isomers (PEP015 or PEP025) in any samples assayed.
|
SECONDARY outcome
Timeframe: baseline and day 57Number of participants with complete clearence. Complete clearance rate is defined as no clinically visible actinic keratosis (AK) lesions in a 25 cm\^2 area within the selected treatment area at Day 57 compared to baseline
Outcome measures
| Measure |
PEP005 Gel, 0.05%
n=13 Participants
PEP005 (ingenol mebutate) Gel 0.05% once daily for 2 consecutive days
|
Vehicle
n=3 Participants
Vehicle gel once daily for 2 consecutive days
|
|---|---|---|
|
Complete Clearance Rate in a 25 cm^2 Area Within the Selected Treatment Area
|
10 participants
|
0 participants
|
SECONDARY outcome
Timeframe: Baseline and Day 57Percentage (%) change in actinic keratosis (AK) lesions count at Day 57, compared to baseline, in a 25 cm\^2 area within the selected treatment area.
Outcome measures
| Measure |
PEP005 Gel, 0.05%
n=13 Participants
PEP005 (ingenol mebutate) Gel 0.05% once daily for 2 consecutive days
|
Vehicle
n=3 Participants
Vehicle gel once daily for 2 consecutive days
|
|---|---|---|
|
Percentage (%) Change in Actinic Keratosis (AK) Lesions in a 25 cm^2 Area Within the Selected Treatment Area
|
-96 change from baseline lesion count (%)
Standard Deviation 8
|
33 change from baseline lesion count (%)
Standard Deviation 58
|
SECONDARY outcome
Timeframe: baseline and Day 2, 3, 8, 15, 29 and 57Number of patients with LSR at any time point during the study above 0. The treatment area was assessed at baseline and at each subsequent study visit for the presence and grade of the following Local Skin Responses (LSRs): erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration using the Local Skin Response Grading Scale (version 5). Each LSR was graded from 0 (best outcome) to 4 (worst outcome). A composite LSR score was calculated as the sum of each individual LSR grade, giving a possible range of 0-24.
Outcome measures
| Measure |
PEP005 Gel, 0.05%
n=13 Participants
PEP005 (ingenol mebutate) Gel 0.05% once daily for 2 consecutive days
|
Vehicle
n=3 Participants
Vehicle gel once daily for 2 consecutive days
|
|---|---|---|
|
Number of Patients With Local Skin Responses (LSRs) Above 0 at Any Time Point During the Study.
|
13 participants
|
1 participants
|
SECONDARY outcome
Timeframe: Baseline, Day 2, 3, 8, 15, 29 and 57Patients with Incidence of pigmentation and scarring, and grade of pigmentation and scarring, following study treatment through Day 57
Outcome measures
| Measure |
PEP005 Gel, 0.05%
n=13 Participants
PEP005 (ingenol mebutate) Gel 0.05% once daily for 2 consecutive days
|
Vehicle
n=3 Participants
Vehicle gel once daily for 2 consecutive days
|
|---|---|---|
|
Patients With Incidence of Pigmentation and Scarring
|
0 participants
|
0 participants
|
SECONDARY outcome
Timeframe: Day 3Max composite Local Skin Response (LSR) score on day 3 only . The treatment area was assessed at baseline and at each subsequent study visit for the presence and grade of the following Local Skin Responses (LSRs): erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration using the Local Skin Response Grading Scale (version 5). Each LSR was graded from 0 (best outcome) to 4 (worst outcome). A composite LSR score was calculated as the sum of each individual LSR grade, giving a possible range of 0-24. (One vehicle treated patent had a LSR on day 1 only).
Outcome measures
| Measure |
PEP005 Gel, 0.05%
n=13 Participants
PEP005 (ingenol mebutate) Gel 0.05% once daily for 2 consecutive days
|
Vehicle
n=3 Participants
Vehicle gel once daily for 2 consecutive days
|
|---|---|---|
|
Max Composite Local Skin Response (LSR) Score
|
6.6 local skin response score
Standard Deviation 3.1
|
0 local skin response score
Standard Deviation 0
|
Adverse Events
PEP005 Gel, 0.05%
Vehicle
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
PEP005 Gel, 0.05%
n=13 participants at risk
PEP005 (ingenol mebutate) Gel 0.05% once daily for 2 consecutive days
|
Vehicle
n=3 participants at risk
Vehicle gel once daily for 2 consecutive days
|
|---|---|---|
|
Gastrointestinal disorders
Toothache
|
7.7%
1/13 • 57 days
|
0.00%
0/3 • 57 days
|
|
Infections and infestations
Sinusitis
|
7.7%
1/13 • 57 days
|
0.00%
0/3 • 57 days
|
|
Injury, poisoning and procedural complications
Arthropod bite
|
7.7%
1/13 • 57 days
|
0.00%
0/3 • 57 days
|
|
Injury, poisoning and procedural complications
Joint sprain
|
7.7%
1/13 • 57 days
|
0.00%
0/3 • 57 days
|
|
Investigations
Gamma-glutamyltransferase increased
|
7.7%
1/13 • 57 days
|
0.00%
0/3 • 57 days
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/13 • 57 days
|
33.3%
1/3 • 57 days
|
|
Infections and infestations
Upper respiratory tract infection
|
0.00%
0/13 • 57 days
|
33.3%
1/3 • 57 days
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Evaluator and Principal Investigator agree not to individually publish the result of the study, but rather, to participate in a joint publication of the Study results coordinated by sponsor, who shall have the first righ to publish. If such joint publication is not submitted for publication within 1 year of study completion at all sites Evaluator and Principal Investigator have the right to individually produce and submit a proposed publication, subject to the prior review of sponsor.
- Publication restrictions are in place
Restriction type: OTHER