Plaque Psoriasis
Conditions
Brief summary
This study will evaluate the incidence of erythema and other local cutaneous irritation after administration of MK-0873 by patch or cream formulation in healthy participants and participants with mild psoriasis. Part I and Part II in healthy participants will be initiated prior to Part III in psoriasis participants. The primary hypotheses of the study are: 1) that MK-0873 is safe and well tolerated in healthy participants and participants with psoriasis and 2) that the maximum plasma concentration of MK-0873 is \<20 nM in healthy participants and participants with psoriasis.
Interventions
DRUGMK-0873 Patch
MK-0873 skin patches containing 0.05%. 0.5%, or 2% MK-0873
DRUGMK-0873 Cream
MK-0873 cream containing 0.05%, 0.5%, or 2% MK-0873
DRUGPlacebo Patch
Placebo patches matching MK-0873 0.05%, 0.5%, or 2% patches
DRUGPlacebo Cream
Placebo cream matching MK-0873 0.05%, 0.5%, or 2%
DRUGPlain patch
Plain patch containing no MK-0873 or placebo
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
Part I, II and III: * Female participants of reproductive potential must test negative for pregnancy and agree to use two acceptable methods of birth control; * In good general health; * Nonsmoker; Part III only: * Has diagnosis of plaque-type psoriasis, and has lesions covering at least 3% of total body surface area;
Exclusion criteria
Part I, II and III: * Has a history of stroke, chronic seizures or major neurological disease; * Has a history of cancer; * Is a nursing mother; Part III only: * Has nonplaque forms of psoriasis; * Has current drug-induced psoriasis; * Has received phototherapy, systemic medications/treatments, or used topical medication that could affect psoriasis; * Has used any systemic immunosuppressants or biologics within the past 4 weeks.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With an Adverse Event of Erythema in Part I of the Study | Up to Day 22 in Part 1 | Following topical administration of MK-0873 or matching placebo patches once daily for 21 days, the number of participants with an adverse event of erythema was recorded. An adverse event is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. |
| Mean Maximum Plasma Concentration (Cmax) of MK-0873 Following Topical Administration for 10 Days | Day 11 | Participant blood samples were collected on Day 11 to determine the Cmax of MK-0873 following topical administration in healthy participants and participants with psoriasis |
| Number of Participants With an Adverse Event | Up to 14 days after last dose of study drug (up to Day 42) | An adverse event is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. |
| Number of Participants Who Discontinued Study Medication Due to an Adverse Event | Up to Day 28 | An adverse event is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Panel A - MK-0873 5.1 mg In Part I, healthy participants received skin patches containing nothing (plain patches), placebo, and various potencies of MK-0873 cream (0.05%, 0.5%, or 2%; yielding a dose of 5.1 mg MK-0873) once daily for 21 days. | 7 |
| Panel A - Placebo In Part I, healthy participants received skin patches containing nothing (plain patch) and placebo once daily for 21 days | 2 |
| Panel B - MK-0873 25 mg In Part II, healthy participants received skin application of 0.5% MK-0873 cream (yielding a dose of 25 mg of MK-0873) twice daily for 10 days. | 6 |
| Panel B - Placebo In Part II, healthy participants received skin application of placebo cream twice daily for 10 days. | 2 |
| Panel C - MK-0873 100 mg In Part II, healthy participants received skin application of 2% MK-0873 cream (yielding a dose of 100 mg of MK-0873) once daily for 10 days. | 6 |
| Panel C - Placebo In Part II, healthy participants received skin application of placebo cream once daily for 10 days. | 2 |
| Panel D - MK-0873 200 mg In Part II, healthy participants received skin application of 2% MK-0873 (yielding a dose of 100 mg of MK-0873) twice daily for 10 days | 6 |
| Panel D - Placebo In Part II, healthy participants received skin application of placebo cream twice daily for 10 days. | 2 |
| Panel E and Extension - MK-0873 200 mg In Part III, participants with mild psoriasis received skin application of 2% MK-0873 cream (yielding a dose of 100 mg of MK-0873) twice daily for up to 28 days. | 7 |
| Panel E and Extension - Placebo In Part III, participants with mild psoriasis received skin application of placebo cream twice daily for up to 28 days. | 2 |
| Total | 42 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Extension | Laboratory Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Part I | Adverse Event | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Panel D - MK-0873 200 mg | Panel A - MK-0873 5.1 mg | Panel A - Placebo | Panel B - MK-0873 25 mg | Panel B - Placebo | Panel C - MK-0873 100 mg | Panel C - Placebo | Panel D - Placebo | Panel E and Extension - MK-0873 200 mg | Panel E and Extension - Placebo | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 30.33 Years FULL_RANGE 6.77 | 42.71 Years FULL_RANGE 12.19 | 30.50 Years FULL_RANGE 17.68 | 40.00 Years FULL_RANGE 11.78 | 45.50 Years FULL_RANGE 14.85 | 45.67 Years FULL_RANGE 12.79 | 34.00 Years FULL_RANGE 7.07 | 35.50 Years FULL_RANGE 2.12 | 42.86 Years FULL_RANGE 11.33 | 40.00 Years FULL_RANGE 15.56 | 39.67 Years FULL_RANGE 11.49 |
| Sex: Female, Male Female | 4 Participants | 5 Participants | 1 Participants | 3 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 5 Participants | 1 Participants | 22 Participants |
| Sex: Female, Male Male | 2 Participants | 2 Participants | 1 Participants | 3 Participants | 1 Participants | 5 Participants | 2 Participants | 1 Participants | 2 Participants | 1 Participants | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 7 | 3 / 6 | 4 / 6 | 6 / 6 | 6 / 7 | 4 / 10 |
| serious Total, serious adverse events | 0 / 7 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 7 | 0 / 10 |
Outcome results
Primary
Mean Maximum Plasma Concentration (Cmax) of MK-0873 Following Topical Administration for 10 Days
Participant blood samples were collected on Day 11 to determine the Cmax of MK-0873 following topical administration in healthy participants and participants with psoriasis
Time frame: Day 11
Population: The population consisted of all enrolled participants who received MK-0873 and for whom blood samples were collected and evaluable to determine Cmax.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Panel A - MK-0873 5.1 mg | Mean Maximum Plasma Concentration (Cmax) of MK-0873 Following Topical Administration for 10 Days | NA nM | — |
| Panel A - Placebo | Mean Maximum Plasma Concentration (Cmax) of MK-0873 Following Topical Administration for 10 Days | 9.10 nM | Standard Deviation 1.52 |
| Panel C - MK-0873 100 mg | Mean Maximum Plasma Concentration (Cmax) of MK-0873 Following Topical Administration for 10 Days | 5.22 nM | Standard Deviation 2.97 |
| Panel D - MK-0873 200 mg | Mean Maximum Plasma Concentration (Cmax) of MK-0873 Following Topical Administration for 10 Days | 12.0 nM | Standard Deviation 3.41 |
| Panel E and Extension - MK-0873 200 mg | Mean Maximum Plasma Concentration (Cmax) of MK-0873 Following Topical Administration for 10 Days | 9.76 nM | Standard Deviation 6.42 |
Primary
Number of Participants Who Discontinued Study Medication Due to an Adverse Event
An adverse event is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.
Time frame: Up to Day 28
Population: The population consisted of all enrolled participants who received at least one dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Panel A - MK-0873 5.1 mg | Number of Participants Who Discontinued Study Medication Due to an Adverse Event | 1 Participants |
| Panel A - Placebo | Number of Participants Who Discontinued Study Medication Due to an Adverse Event | 0 Participants |
| Panel C - MK-0873 100 mg | Number of Participants Who Discontinued Study Medication Due to an Adverse Event | 0 Participants |
| Panel D - MK-0873 200 mg | Number of Participants Who Discontinued Study Medication Due to an Adverse Event | 0 Participants |
| Panel E and Extension - MK-0873 200 mg | Number of Participants Who Discontinued Study Medication Due to an Adverse Event | 0 Participants |
| Placebo - Pooled | Number of Participants Who Discontinued Study Medication Due to an Adverse Event | 0 Participants |
Primary
Number of Participants With an Adverse Event
An adverse event is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.
Time frame: Up to 14 days after last dose of study drug (up to Day 42)
Population: The population consisted of all enrolled participants who received at least one dose of study medication for whom safety data were available.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Panel A - MK-0873 5.1 mg | Number of Participants With an Adverse Event | 3 Participants |
| Panel A - Placebo | Number of Participants With an Adverse Event | 3 Participants |
| Panel C - MK-0873 100 mg | Number of Participants With an Adverse Event | 4 Participants |
| Panel D - MK-0873 200 mg | Number of Participants With an Adverse Event | 6 Participants |
| Panel E and Extension - MK-0873 200 mg | Number of Participants With an Adverse Event | 6 Participants |
| Placebo - Pooled | Number of Participants With an Adverse Event | 4 Participants |
Primary
Number of Participants With an Adverse Event of Erythema in Part I of the Study
Following topical administration of MK-0873 or matching placebo patches once daily for 21 days, the number of participants with an adverse event of erythema was recorded. An adverse event is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.
Time frame: Up to Day 22 in Part 1
Population: The population consisted of all enrolled participants who received at least one dose of study medication in Part I of the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Panel A - MK-0873 5.1 mg | Number of Participants With an Adverse Event of Erythema in Part I of the Study | 0 Participants |
| Panel A - Placebo | Number of Participants With an Adverse Event of Erythema in Part I of the Study | 0 Participants |