Psoriasis Vulgaris
Conditions
Brief summary
This is a phase 2, randomised, open-label, parallel-group, multicentre trial in which MC2-01 cream and calcipotriene \[CAL\]/betamethasone \[BDP\] ointment (comparator) is investigated in subjects with clinically diagnosed extensive psoriasis vulgaris.
Detailed description
The MC2-01 cream is designed for optimal patient satisfaction - it quickly absorbs into the skin leaving it nicely moisturized allowing patients to move on with daily routines. In this trial, the MC2-01 cream will be compared to a marketed calcipotriene \[CAL\]/betamethasone dipropionate \[BDP\] ointment. The purpose of the trial, is to determine the pharmacokinetic parameters of MC2-01 cream and the comparator under maximum use conditions.
Interventions
DRUGMC2-01 Cream
MC2-01 (calcipotriene/betamethasone dipropionate, w/w 0.005%/0.064%)
Calcipotriene/betamethasone (calcipotriene/ betamethasone dipropionate, w/w 0.005%/0.064%)
Sponsors
MC2 Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Have provided written informed consent. * Generally healthy males or non-pregnant females, of any race or ethnicity, who are at least 18 years of age at the time of screening. * At Visit 1/Day 0, have a clinical diagnosis of plaque psoriasis (psoriasis vulgaris) of at least 6 months duration involving scalp and body (trunk and/or limbs) that is amenable to topical treatment with a maximum of 100 g of trial medication per week. * Have a Physician's Global Assessment \[PGA\] of severity of at least moderate on the trunk, limbs and/or scalp, at Visit 1/Day 0. * Have a treatment area between 20% and 30% of the body surface area \[BSA\] on the trunk, limbs and/or scalp, excluding psoriatic lesions on the face, genitals, and intertriginous areas, at Visit 1/Day 0.
Exclusion criteria
* Current diagnosis of unstable forms of psoriasis * Other inflammatory skin disease in the treatment area * Pigmentation, extensive scarring, pigmented lesions or sunburn in the treatment areas * Planned exposure to natural or artificial sunlight * Phototherapy and ultraviolet B radiation within 4 weeks prior to Visit 1/Baseline and during the trial; * Current or past history of hypercalcemia, vitamin D toxicity, severe renal insufficiency, or severe hepatic disorders; * Oral calcium supplements, vitamin D supplements, bisphosphonates or calcitonin within 4 weeks prior to Visit 1/Day 0 during the trial period. * Planned initiation of, or changes to concomitant medication that could affect calcium metabolism during the trial; * Planned initiation of, or changes to, concomitant estrogen therapy during the trial; * Strong systemic cytochrome P450 3A4 (CYP 3A4) inhibitors within 4 weeks prior to Vist 1/Day 0 and during the trial period; * Use of topical treatments, except for emollients and non-medicated shampoos, with a possible effect on psoriasis within 2 weeks prior to Visit 1/Day 0 and during the trial period; * Systemic treatment with biological therapies * Initiation of, or expected changes to, concomitant medication that may affect psoriasis during the trial period; * Depression and endocrine disorders known to affect cortisol levels or HPA axis integrity, non-nocturnal sleep patterns * Systemic medication that suppresses the immune system within 4 weeks prior to the Visit 1/Day 0 and during the trial period; * Clinical signs of skin infection with bacteria, viruses, or fungi; * Known human immunodeficiency virus \[HIV\] infection; * Known or suspected of hypersensitivity to any component of the test product or reference product; * Any chronic or acute medical condition that may pose a risk to the safety of the subject, or may interfere with the assessment of safety or efficacy in this trial;
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Plasma Concentration (Cmax) of the Active Ingredient Calcipotriene | Week 4 | Geometric Mean for Maximum Plasma Concentration \[Cmax\] for the active ingredient Calcipotriene. Plasma concentration was measured at the following timepoints: pre-dose, 30 min, 1, 2, 3, 5 and 7 hours post-dose |
| Maximum Plasma Concentration (Cmax) of Active Ingredient Betamethasone Dipropionate | Week 4 | Geometric Mean for Maximum Plasma Concentration \[Cmax\] for the active ingredient Betamethasone Dipropionate. Plasma concentration was measured at the following timepoints: pre-dose, 30 min, 1, 2, 3, 5 and 7 hours post-dose |
| Maximum Plasma Concentration (Cmax) of the Metabolite MC1080 | Week 4 | Geometric Mean for Maximum Plasma Concentration \[Cmax\] for the metabolite MC1080. Plasma concentration was measured at the following timepoints: pre-dose, 30 min, 1, 2, 3, 5 and 7 hours post-dose |
| Maximum Plasma Concentration (Cmax) of Metabolite Betamethasone 17-propionate | Week 4 | Geometric Mean for Maximum Plasma Concentration \[Cmax\] for the metabolite Betamethasone 17-propionate. Plasma concentration was measured at the following timepoints: pre-dose, 30 min, 1, 2, 3, 5 and 7 hours post-dose |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Hypothalamic-pituitary-adrenal [HPA] Suppression After 4 Weeks of Treatment | Week 4 | The HPA axis evaluation is based on an Adrenocorticotropic hormone \[ACTH\] challenge test, defined by a 30 minutes ACTH stimulated cortisol value. Only subject with no HPA suppression at baseline were included in the analysis. The outcome measure lists the number of subjects with HPA suppression 30 minutes after ACTH challenge |
| Calcium Metabolism Evaluation of the Ratio of Urinary Calcium to Creatinine | Baseline and week 4 | Changes from baseline in ratio of urinary calcium to creatinine defined as urinary calcium (mmol)/creatinine (g) |
| Number of Subjects With Hypothalamic-pituitary-adrenal [HPA] Suppression After 8 Weeks of Treatment | Week 8 | The HPA challenge test were only performed on subjects that were assigned to the MC2-01 cream group. Out of a total of 32 subjects, 5 subjects were excluded from the analysis as they had HPA suppression at baseline |
| Calcium Metabolism Evaluation in Albumin-corrected Serum Calcium | Baseline and week 4 | Changes from baseline of albumin-corrected serum calcium \[mmol/L\] |
| Calcium Metabolism Evaluation of 24-hour Urinary Calcium Excretion | Baseline and week 4 | Changes from baseline of 24-hour urinary calcium excretion \[mmol/day\] |
Countries
United States
Participant flow
Recruitment details
First Subject First Visit: 08Feb-2018. Last Subject Last Visit: 04-Aug-2018.
Pre-assignment details
Prior to randomization, the subject entered a washout period (if required) where anti-psoriatic treatment and other relevant medication/treatments were discontinued as defined by the exclusion criteria. The washout/screening period lasted for up to 4 weeks depending on which disallowed treatments the subject received.
Participants by arm
| Arm | Count |
|---|---|
| MC2-01 Cream MC2-01 cream (CAL and BDP, w/w 0.005%/ 0.064%).
MC2-01 Cream: MC2-01 (calcipotriene/betamethasone dipropionate, w/w 0.005%/0.064%) | 32 |
| CAL/BDP Combination CAL/BDP ointment (w/w 0.005%/0.064%).
CAL/BDP combination: Calcipotriene/betamethasone (calcipotriene/ betamethasone dipropionate, w/w 0.005%/0.064%) | 31 |
| Total | 63 |
Baseline characteristics
| Characteristic | CAL/BDP Combination | MC2-01 Cream | Total |
|---|---|---|---|
| Age, Continuous | 49.7 years STANDARD_DEVIATION 16.2 | 52.8 years STANDARD_DEVIATION 15.5 | 51.3 years STANDARD_DEVIATION 15.8 |
| Baseline Body Surface Area (BSA) | 24.09 Percentage of psoriasis involvement STANDARD_DEVIATION 3.13 | 23.56 Percentage of psoriasis involvement STANDARD_DEVIATION 2.52 | 23.82 Percentage of psoriasis involvement STANDARD_DEVIATION 2.82 |
| Baseline Physician's Global Assessment (PGA) Moderate | 30 Participants | 29 Participants | 59 Participants |
| Baseline Physician's Global Assessment (PGA) Severe | 1 Participants | 3 Participants | 4 Participants |
| Fitzpatrick Skin Type I | 2 Participants | 3 Participants | 5 Participants |
| Fitzpatrick Skin Type II | 9 Participants | 11 Participants | 20 Participants |
| Fitzpatrick Skin Type III | 6 Participants | 8 Participants | 14 Participants |
| Fitzpatrick Skin Type IV | 9 Participants | 5 Participants | 14 Participants |
| Fitzpatrick Skin Type V | 5 Participants | 3 Participants | 8 Participants |
| Fitzpatrick Skin Type VI | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 2 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 28 Participants | 28 Participants | 56 Participants |
| Region of Enrollment United States | 31 participants | 32 participants | 63 participants |
| Sex: Female, Male Female | 21 Participants | 19 Participants | 40 Participants |
| Sex: Female, Male Male | 10 Participants | 13 Participants | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 32 | 0 / 31 |
| other Total, other adverse events | 0 / 32 | 0 / 31 |
| serious Total, serious adverse events | 0 / 32 | 1 / 31 |
Outcome results
Primary
Maximum Plasma Concentration (Cmax) of Active Ingredient Betamethasone Dipropionate
Geometric Mean for Maximum Plasma Concentration \[Cmax\] for the active ingredient Betamethasone Dipropionate. Plasma concentration was measured at the following timepoints: pre-dose, 30 min, 1, 2, 3, 5 and 7 hours post-dose
Time frame: Week 4
Population: 9 subjects were excluded from the PK evaluation at Week 4: 5 in the MC2-01 cream group and 4 in the active comparator group
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| MC2-01 Cream | Maximum Plasma Concentration (Cmax) of Active Ingredient Betamethasone Dipropionate | 21.5 pg/mL |
| CAL/BDP Ointment | Maximum Plasma Concentration (Cmax) of Active Ingredient Betamethasone Dipropionate | 23.1 pg/mL |
Primary
Maximum Plasma Concentration (Cmax) of Active Ingredient Betamethasone Dipropionate
Geometric Mean for Maximum Plasma Concentration \[Cmax\] for the active ingredient Betamethasone Dipropionate. Plasma concentration was measured at the following timepoints: pre-dose, 30 min, 1, 2, 3, 5 and 7 hours post-dose
Time frame: Week 8
Population: As per protocol, only subjects assigned to the MC2-01 cream had samples for PK testing collected at week 8. Only subjects that had a computable value of the PK parameter have been included in the analysis
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| MC2-01 Cream | Maximum Plasma Concentration (Cmax) of Active Ingredient Betamethasone Dipropionate | 20.0 pg/mL |
Primary
Maximum Plasma Concentration (Cmax) of Metabolite Betamethasone 17-propionate
Geometric Mean for Maximum Plasma Concentration \[Cmax\] for the metabolite Betamethasone 17-propionate. Plasma concentration was measured at the following timepoints: pre-dose, 30 min, 1, 2, 3, 5 and 7 hours post-dose
Time frame: Week 8
Population: As per protocol, only subjects assigned to the MC2-01 cream had samples for PK testing collected at week 8. Only subjects that had a computable value of the PK parameter have been included in the analysis
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| MC2-01 Cream | Maximum Plasma Concentration (Cmax) of Metabolite Betamethasone 17-propionate | 26.2 pg/mL |
Primary
Maximum Plasma Concentration (Cmax) of Metabolite Betamethasone 17-propionate
Geometric Mean for Maximum Plasma Concentration \[Cmax\] for the metabolite Betamethasone 17-propionate. Plasma concentration was measured at the following timepoints: pre-dose, 30 min, 1, 2, 3, 5 and 7 hours post-dose
Time frame: Week 4
Population: 9 subjects were excluded from the PK evaluation at Week 4: 5 in the MC2-01 cream group and 4 in active comparator group
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| MC2-01 Cream | Maximum Plasma Concentration (Cmax) of Metabolite Betamethasone 17-propionate | 39.3 pg/mL |
| CAL/BDP Ointment | Maximum Plasma Concentration (Cmax) of Metabolite Betamethasone 17-propionate | 38.2 pg/mL |
Primary
Maximum Plasma Concentration (Cmax) of the Active Ingredient Calcipotriene
Geometric Mean for Maximum Plasma Concentration \[Cmax\] for the active ingredient Calcipotriene. Plasma concentration was measured at the following timepoints: pre-dose, 30 min, 1, 2, 3, 5 and 7 hours post-dose
Time frame: Week 4
Population: 9 subjects were excluded from the PK evaluation at Week 4: 5 in the MC2-01 cream group and 4 in the active comparator group
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| MC2-01 Cream | Maximum Plasma Concentration (Cmax) of the Active Ingredient Calcipotriene | 30.2 pg/mL |
| CAL/BDP Ointment | Maximum Plasma Concentration (Cmax) of the Active Ingredient Calcipotriene | 30.0 pg/mL |
Primary
Maximum Plasma Concentration (Cmax) of the Active Ingredient Calcipotriene
Geometric Mean for Maximum Plasma Concentration \[Cmax\] for the active ingredient Calcipotriene. Plasma concentration was measured at the following timepoints: pre-dose, 30 min, 1, 2, 3, 5 and 7 hours post-dose
Time frame: Week 8
Population: As per protocol, only subjects assigned to the MC2-01 cream had samples for PK testing collected at week 8. Only subjects that had a computable value of the PK parameter have been included in the analysis
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| MC2-01 Cream | Maximum Plasma Concentration (Cmax) of the Active Ingredient Calcipotriene | 30.0 pg/mL |
Primary
Maximum Plasma Concentration (Cmax) of the Metabolite MC1080
Geometric Mean for Maximum Plasma Concentration \[Cmax\] for the metabolite MC1080. Plasma concentration was measured at the following timepoints: pre-dose, 30 min, 1, 2, 3, 5 and 7 hours post-dose
Time frame: Week 8
Population: As per protocol, only subjects assigned to the MC2-01 cream had samples for PK testing collected at week 8. Only subjects that had a computable value of the PK parameter have been included in the analysis
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| MC2-01 Cream | Maximum Plasma Concentration (Cmax) of the Metabolite MC1080 | 29.1 pg/mL |
Primary
Maximum Plasma Concentration (Cmax) of the Metabolite MC1080
Geometric Mean for Maximum Plasma Concentration \[Cmax\] for the metabolite MC1080. Plasma concentration was measured at the following timepoints: pre-dose, 30 min, 1, 2, 3, 5 and 7 hours post-dose
Time frame: Week 4
Population: 9 subjects were excluded from the PK evaluation at Week 4: 5 in the MC2-01 cream group and 4 in active comparator group
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| MC2-01 Cream | Maximum Plasma Concentration (Cmax) of the Metabolite MC1080 | 29.8 pg/mL |
| CAL/BDP Ointment | Maximum Plasma Concentration (Cmax) of the Metabolite MC1080 | 29.2 pg/mL |
Secondary
Calcium Metabolism Evaluation in Albumin-corrected Serum Calcium
Changes from baseline in albumin-corrected serum calcium \[mmol/L\]
Time frame: Baseline and week 8
Population: As per protocol, only subjects assigned to the MC2-01 cream were included in the calcium metabolism evaluation. No data were collected from the CAL/BDP Ointment group. 6 subjects in the MC2-01 cream group were excluded from the analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MC2-01 Cream | Calcium Metabolism Evaluation in Albumin-corrected Serum Calcium | 0.00 mmol/L | Standard Deviation 0.07 |
Secondary
Calcium Metabolism Evaluation in Albumin-corrected Serum Calcium
Changes from baseline of albumin-corrected serum calcium \[mmol/L\]
Time frame: Baseline and week 4
Population: As per protocol, only subjects assigned to the MC2-01 cream were included in the calcium metabolism evaluation. No data were collected from the CAL/BDP Ointment group. 5 subjects in the MC2-01 cream group were excluded from the analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MC2-01 Cream | Calcium Metabolism Evaluation in Albumin-corrected Serum Calcium | -0.00 mmol/L | Standard Deviation 0.09 |
Secondary
Calcium Metabolism Evaluation of 24-hour Urinary Calcium Excretion
Changes from baseline of 24-hour urinary calcium excretion \[mmol/day\]
Time frame: Baseline and week 4
Population: As per protocol, only subjects assigned to the MC2-01 cream were included in the calcium metabolism evaluation. No data were collected from the CAL/BDP Ointment group. 8 subjects in the MC2-01 cream group were excluded from the analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MC2-01 Cream | Calcium Metabolism Evaluation of 24-hour Urinary Calcium Excretion | -0.56 mmol/day | Standard Deviation 1.69 |
Secondary
Calcium Metabolism Evaluation of 24-hour Urinary Calcium Excretion
Changes from baseline of 24-hour urinary calcium excretion \[mmol/day\]
Time frame: Baseline and week 8
Population: As per protocol, only subjects assigned to the MC2-01 cream were included in the calcium metabolism evaluation. No data were collected from the CAL/BDP Ointment group. 12 subjects in the MC2-01 cream group were excluded from the analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MC2-01 Cream | Calcium Metabolism Evaluation of 24-hour Urinary Calcium Excretion | -0.45 mmol/day | Standard Deviation 1.08 |
Secondary
Calcium Metabolism Evaluation of the Ratio of Urinary Calcium to Creatinine
Changes from baseline in ratio of urinary calcium to creatinine defined as urinary calcium (mmol)/creatinine (g)
Time frame: Baseline and week 8
Population: As per protocol, only subjects assigned to the MC2-01 cream were included in the calcium metabolism evaluation. No data were collected from the CAL/BDP Ointment group. 12 subjects in the MC2-01 cream group were excluded from the analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MC2-01 Cream | Calcium Metabolism Evaluation of the Ratio of Urinary Calcium to Creatinine | 0.00 mmol/g | Standard Deviation 1.32 |
Secondary
Calcium Metabolism Evaluation of the Ratio of Urinary Calcium to Creatinine
Changes from baseline in ratio of urinary calcium to creatinine defined as urinary calcium (mmol)/creatinine (g)
Time frame: Baseline and week 4
Population: As per protocol, only subjects assigned to the MC2-01 cream were included in the calcium metabolism evaluation. No data were collected from the CAL/BDP Ointment group. 8 subjects in the MC2-01 cream group were excluded from the analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MC2-01 Cream | Calcium Metabolism Evaluation of the Ratio of Urinary Calcium to Creatinine | -0.23 mmol/g | Standard Deviation 1.49 |
Secondary
Number of Subjects With Hypothalamic-pituitary-adrenal [HPA] Suppression After 4 Weeks of Treatment
The HPA axis evaluation is based on an Adrenocorticotropic hormone \[ACTH\] challenge test, defined by a 30 minutes ACTH stimulated cortisol value. Only subject with no HPA suppression at baseline were included in the analysis. The outcome measure lists the number of subjects with HPA suppression 30 minutes after ACTH challenge
Time frame: Week 4
Population: The HPA challenge test were only performed on subjects that were assigned to the MC2-01 cream group. No data were collected from the CAL/BDP Ointment group. Out of a total of 32 subjects, 5 subjects were excluded from the analysis as they had HPA suppression at baseline
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| MC2-01 Cream | Number of Subjects With Hypothalamic-pituitary-adrenal [HPA] Suppression After 4 Weeks of Treatment | 1 Participants |
Secondary
Number of Subjects With Hypothalamic-pituitary-adrenal [HPA] Suppression After 8 Weeks of Treatment
The HPA challenge test were only performed on subjects that were assigned to the MC2-01 cream group. Out of a total of 32 subjects, 5 subjects were excluded from the analysis as they had HPA suppression at baseline
Time frame: Week 8
Population: The HPA challenge test were only performed on subjects that were assigned to the MC2-01 cream group. No data were collected from the CAL/BDP Ointment group. Out of a total of 32 subjects, 6 subjects were excluded from the analysis; 5 as they had HPA suppression at baseline and 1 who withdrew consent
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| MC2-01 Cream | Number of Subjects With Hypothalamic-pituitary-adrenal [HPA] Suppression After 8 Weeks of Treatment | 2 Participants |