Psoriasis Vulgaris
Conditions
Brief summary
An international, multi-centre, prospective, non-controlled, open, single-group, 8-week trial in adolescent subjects (aged 12 to 16 years, 11 months) with scalp and body psoriasis.
Detailed description
A phase 2 trial evaluating the safety and efficacy of once daily use of LEO 80185 gel containing calcipotriol 50 mcg/g plus betamethasone 0.5mg/g (as dipropionate) in adolescent subjects (aged 12 to 16 years, 11 months) with scalp and body psoriasis.
Interventions
DRUGLEO 80185 gel
Sponsors
LEO Pharma
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
(all subjects): * Clinical signs of psoriasis vulgaris on both the scalp and body (trunk and/or limbs) * At SV2 and Visit 1, a clinical diagnosis of scalp and body (trunk and/or limbs) psoriasis which is: * of an extent of 10 to 35% of the body surface area (excluding psoriatic lesions of the face and sensitive areas. Sensitive areas include armpits, groin, under the breasts and in other skin folds around the genitals and buttocks), and * of at least moderate severity according to the investigator's global assessment of disease severity on the body. * A serum albumin-corrected calcium level below the upper reference limit at SV2 Inclusion Criteria (for subjects performing HPA axis assessments): * At SV2 and Visit 1, a clinical diagnosis of scalp psoriasis which is: * more than or equal to 20% of the scalp area, and * of at least moderate severity according to the investigator's global assessment of disease severity on the scalp. * Subjects with a normal HPA axis function at SV2 including serum cortisol concentration above 5 mcg/dl before ACTH challenge and serum cortisol concentration above 18 mcg/dl 30 minutes after ACTH challenge. Inclusion Criteria (for subjects not performing HPA axis assessments): * At SV2 and Visit 1, a clinical diagnosis of scalp psoriasis which is: * more than or equal to 10% of the scalp area, and * of at least moderate severity according to the investigator's global assessment of disease severity on the scalp.
Exclusion criteria
(all subjects): * Systemic treatment with biological therapies (marketed or not marketed), with a possible effect on scalp and/or body psoriasis within the following time period prior to Visit 1 and during the trial: * etanercept - within 4 weeks prior to Visit 1 * adalimumab, infliximab - within 2 months prior to Visit 1 * ustekinumab - within 4 months prior to Visit 1 * experimental products - within 4 weeks/5 half-lives (whichever is longer) prior to Visit 1 * Systemic treatment with therapies other than biologicals, with a possible effect on scalp and/or body psoriasis (e.g., retinoids, immunosuppressants, PUVA) within 4 weeks prior to Visit 1 (Day 0) or during the trial. * UVB therapy within 2 weeks prior to Visit 1 or during the trial. * Any topical treatment on the scalp and body (except for emollients and non-steroid medicated shampoos) within 2 weeks prior to Visit 1 or during the trial. * Systemic calcium, vitamin D supplements, antacids, diuretics, antiepileptics, diphosphonates or calcitonin within 4 weeks prior to SV2 or during the trial. * Planned initiation of, or changes to, concomitant medication that could affect psoriasis (e.g., betablockers, chloroquine, lithium, ACE inhibitors) during the trial. * Current diagnosis of guttate, erythrodermic, exfoliative or pustular psoriasis. * Subjects with any of the following conditions present on the treatment areas on scalp and/or body: viral (e.g., herpes or varicella) lesions of the skin, fungal and bacterial skin infections, parasitic infections, skin manifestations in relation to syphilis or tuberculosis, rosacea, acne vulgaris, acne rosacea, atrophic skin, striae atrophicae, fragility of skin veins, ichthyosis, ulcers and wounds. * Other inflammatory skin diseases that may confound the evaluation of scalp and/or body psoriasis. * Planned excessive exposure to sun during the trial that may affect scalp and/or body psoriasis. * Known or suspected severe renal insufficiency or severe hepatic disorders. * Known or suspected disorders of calcium metabolism associated with hypercalcaemia. * Any clinically significant abnormality following review of screening laboratory tests (blood and urine samples), physical examination or blood pressure/heart rate measurement performed at SV2. * Current participation in any other interventional clinical trial. * Previously enrolled in this trial. * Subjects who have received treatment with any non-marketed drug substance (i.e., an agent which has not yet been made available for clinical use following registration) within a month prior to SV1 or longer, if the class of substance required a longer wash-out as defined above (e.g., biological treatments). * Subjects or parent(s) or legal guardian known or suspected of being unlikely to comply with the Clinical Trial Protocol (e.g., alcoholism, drug dependency or psychotic state). * Females who are pregnant, or of child-bearing potential and wishing to become pregnant during the trial, or who are breast-feeding. * Females of child-bearing potential with positive pregnancy test at SV2. * Subject (or their partner) not using an adequate method of contraception according to national requirements.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Drug Reactions (ADRs) | 8 weeks | Number of Adverse Drug Reactions (ADRs) |
| Subjects With Serum Cortisol Concentration of ≤18 mcg/dl at 30 Minutes After ACTH-challenge at Week 4 | 30 minutes after ACTH-challenge at Week 4 | Number of subjects with serum cortisol concentration of ≤18 mcg/dl at 30 minutes after ACTH-challenge at Week 4 |
| Subjects With Serum Cortisol Concentration of ≤18 mcg/dl at 30 Minutes After ACTH-challenge at Week 8 | 30 minutes after ACTH-challenge at Week 8 | Number of subjects with serum cortisol concentration of ≤18 mcg/dl at 30 minutes after ACTH-challenge at Week 8 |
| Change in Albumin-corrected Serum Calcium From Baseline to Week 4 | From baseline to Week 4 | Change in albumin-corrected serum calcium from baseline to Week 4 |
| Change in Albumin-corrected Serum Calcium From Baseline to Week 8 | From baseline to Week 8 | Change in albumin-corrected serum calcium from baseline to Week 8 |
| Change in Albumin-corrected Serum Calcium From Baseline to End of Treatment | From baseline to end of treatment | Change in albumin-corrected serum calcium from baseline to end of treatment, defined as the last value recorded after baseline up to and including Week 8. |
| Change in 24-hour Urinary Calcium Excretion From Baseline to Week 4 | From baseline to Week 4 | Change in 24-hour urinary calcium excretion from baseline to Week 4 |
| Change in 24-hour Urinary Calcium Excretion From Baseline to Week 8 | From baseline to Week 8 | Change in 24-hour urinary calcium excretion from baseline to Week 8 |
| Change in 24-hour Urinary Calcium Excretion From Baseline to End of Treatment | From baseline to end of treatment | Change in 24-hour urinary calcium excretion from baseline to end of treatment, defined as the last value recorded after baseline up to and including Week 8. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic Evaluation C(Max) | Week 4, blood samples taken before IMP was applied and 1, 3, and 5 hours after application of IMP | C(max) values for betamethasone dipropionate, betamethasone 17-propionate, calcipotriol, and MC1080. Betamethasone dipropionate was only detected above lower limit of quantification in 5 samples from 4 subjects and betamethasone 17-propionate was only detected in 12 samples from 5 subjects, therefore pharmacokinetic profiles could not be calculated. Presented C(max) values for betamethasone dipropionate and betamethasone 17-propionate are the the single highest concentrations measured in any sample at any time. Calcipotriol and MC1080 were never detected above lower limit of quantification, therefore no PK parameters could be calculated and no data have been entered for calcipotriol and MC1080. |
| Pharmacokinetic Evaluation T(Max) | Week 4, blood samples taken before IMP was applied and 1, 3, and 5 hours after application of IMP | T(max) values for betamethasone dipropionate, betamethasone 17-propionate, calcipotriol, and MC1080. Betamethasone dipropionate was only detected above lower limit of quantification in 5 samples from 4 subjects and betamethasone 17-propionate was only detected in 12 samples from 5 subjects. Therefore it was not possible to calculate T(max) for betamethasone dipropionate and betamethasone 17-propionate. Calcipotriol and MC1080 were never detected above lower limit of quantification, therefore no PK parameters could be calculated and no data have been entered for calcipotriol and MC1080. |
| Pharmacokinetic Evaluation T(½) | Week 4, blood samples taken before IMP was applied and 1, 3, and 5 hours after application of IMP | T(½) values for betamethasone dipropionate, betamethasone 17-propionate, calcipotriol, and MC1080. Betamethasone dipropionate was only detected above lower limit of quantification in 5 samples from 4 subjects and betamethasone 17-propionate was only detected in 12 samples from 5 subjects, therefore it was not possible to calculate T(½) for betamethasone dipropionate or betamethasone 17-propionate. Calcipotriol and MC1080 were never detected above lower limit of quantification, therefore no PK parameters could be calculated and no data have been entered for calcipotriol and MC1080. |
| Adverse Events (AEs) | 8 weeks | Number of Adverse Events (AEs) |
| Percentage Change in PASI From Baseline to End of Treatment | From baseline to end of treatment | Percentage change in Psoriasis area and severity index (PASI) score from baseline to end of treatment, defined as the last value recorded up to and including Week 8. Psoriasis area and severity index (PASI) assesses extent and severity of clinical signs of psoriasis vulgaris. Body surface is divided in 4 ares: head (incl. neck), arms (incl. hands), trunk (incl. flexures) and legs (incl. buttocks and feet). Each area is scored from 0-6 for extent of psoriasis and from 0-4 for redness, thickness, and scaliness, and an area PASI score is calculated. The total PASI score is calculated from each area's score. The PASI score ranges from 0 (clear skin) to 72 (maximum disease), a PASI score higher than 10 generally corresponds to moderate-to-severe disease. |
| Subjects With Controlled Disease According to the Patient's Global Assessment of Disease Severity on the Body at End of Treatment | End of treatment | Subjects with Controlled disease (i.e., Clear or Almost clear for subjects with at least Moderate disease at baseline, Clear for subjects with Mild disease at baseline) according to the patient's global assessment of disease severity on the body at end of treatment, defined as the last value recorded up to and including Week 8. |
| Subjects With Controlled Disease According to the Investigator's Global Assessment of Disease Severity on the Body at End of Treatment | End of treatment | Subjects with Controlled disease (i.e., Clear or Almost clear for subjects with at least Moderate disease at baseline, Clear for subjects with Mild disease at baseline) according to the investigator's global assessment of disease severity on the body at end of treatment, defined as the last value recorded up to and including Week 8. |
| Subjects With Serum Cortisol Concentration of ≤18 mcg/dl at Both 30 and 60 Minutes After ACTH-challenge at Week 4 | 30 and 60 minutes after ACTH-challenge at Week 4 | Number of subjects with serum cortisol concentration of ≤18 mcg/dl at both 30 and 60 minutes after ACTH-challenge at Week 4 |
| Subjects With Serum Cortisol Concentration of ≤18 mcg/dl at Both 30 and 60 Minutes After ACTH-challenge at Week 8 | 30 and 60 minutes after ACTH-challenge at Week 8 | Number of subjects with serum cortisol concentration of ≤18 mcg/dl at both 30 and 60 minutes after ACTH-challenge at Week 8 |
| Change in Urinary Calcium:Creatinine Ratio From Baseline to Week 4 | From baseline to Week 4 | Change in urinary calcium:creatinine ratio from baseline to Week 4 |
| Change in Urinary Calcium:Creatinine Ratio From Baseline to Week 8 | From baseline to Week 8 | Change in urinary calcium:creatinine ratio from baseline to Week 8 |
| Change in Serum Alkaline Phosphatase From Baseline to Week 4 | From baseline to Week 4 | Change in serum alkaline phosphatase from baseline to Week 4 |
| Change in Serum Alkaline Phosphatase From Baseline to Week 8 | From baseline to Week 8 | Change in serum alkaline phosphatase from baseline to Week 8 |
| Pharmacokinetic Evaluation AUC(0-t) | Week 4, blood samples taken before IMP was applied and 1, 3, and 5 hours after application of IMP | AUC(0-t) values for betamethasone dipropionate, betamethasone 17-propionate, calcipotriol, and MC1080. Betamethasone dipropionate was only detected above lower limit of quantification in 5 samples from 4 subjects, and no subjects had enough positive samples to allow calculation AUC(0-t) for betamethasone dipropionate. Betamethasone 17-propionate was only detected in 12 samples from 5 subjects, and only 2 subjects had enough positive samples to calculate AUC(0-t). The mean value of AUC(0-t) for these 2 subjects is presented for betamethasone 17-propionate. Calcipotriol and MC1080 were never detected above lower limit of quantification, therefore no PK parameters could be calculated and no data have been entered for calcipotriol and MC1080. |
| Pharmacokinetic Evaluation AUC(0-infinity) | Week 4, blood samples taken before IMP was applied and 1, 3, and 5 hours after application of IMP | AUC(0-infinity) values for betamethasone dipropionate, betamethasone 17-propionate, calcipotriol, and MC1080. Betamethasone dipropionate was only detected above lower limit of quantification in 5 samples from 4 subjects, and no subjects had enough positive samples to allow calculation AUC(0-infinity) for betamethasone dipropionate. Betamethasone 17-propionate was only detected in 12 samples from 5 subjects, and only 2 subjects had enough positive samples to calculate AUC(0-infinity). The mean value of AUC(0-infinity) for these 2 subjects is presented for betamethasone 17-propionate. Calcipotriol and MC1080 were never detected above lower limit of quantification, therefore no PK parameters could be calculated and no data have been entered for calcipotriol and MC1080. The terms AUC(0-infinity) and AUC(all) are interchangeable, AUC(0-infinity) was used in the protocol whereas AUC(all) was used in the report. AUC(0-infinity) has been used here to be consistent with the protocol. |
Countries
Canada, France, Germany, Poland, Romania, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| LEO 80185 Gel LEO 80185 gel, containing calcipotriol (50 mcg/g) and betamethasone (0.5 mg/g, as dipropionate), was applied once daily to scalp and body psoriasis lesions. This arm contains all 107 subjects that were assigned to treatment and constitutes the full analysis set and the safety analysis set. 31 subjects in this arm performed additional hypothalamic-pituitary axis assessments and constitute the per protocol analysis set. | 107 |
| Total | 107 |
Baseline characteristics
| Characteristic | LEO 80185 Gel |
|---|---|
| Age, Continuous | 14.2 years STANDARD_DEVIATION 1.4 |
| Duration of psoriasis vulgaris | 4.1 years STANDARD_DEVIATION 3.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 100 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Fitzpatrick Skin Type Type I | 2 Participants |
| Fitzpatrick Skin Type Type II | 47 Participants |
| Fitzpatrick Skin Type Type III | 34 Participants |
| Fitzpatrick Skin Type Type IV | 20 Participants |
| Fitzpatrick Skin Type Type V | 2 Participants |
| Fitzpatrick Skin Type Type VI | 2 Participants |
| Investigator's assessment of extent of psoriasis on the body and scalp (%) | 14.9 % of body surface area affected STANDARD_DEVIATION 8.3 |
| Investigator's global assessment of disease severity on body Mild | 14 Participants |
| Investigator's global assessment of disease severity on body Moderate | 87 Participants |
| Investigator's global assessment of disease severity on body Severe | 6 Participants |
| Patient's global assessment of disease severity on body Mild | 21 Participants |
| Patient's global assessment of disease severity on body Moderate | 77 Participants |
| Patient's global assessment of disease severity on body Severe | 4 Participants |
| Patient's global assessment of disease severity on body Very Mild | 5 Participants |
| Psoriasis Area and Severity Index Score | 10.70 score on a scale STANDARD_DEVIATION 4.41 |
| Race/Ethnicity, Customized Asian | 6 Participants |
| Race/Ethnicity, Customized Black or African American | 2 Participants |
| Race/Ethnicity, Customized Other | 2 Participants |
| Race/Ethnicity, Customized White | 97 Participants |
| Region of Enrollment Canada | 6 participants |
| Region of Enrollment France | 5 participants |
| Region of Enrollment Germany | 20 participants |
| Region of Enrollment Poland | 14 participants |
| Region of Enrollment Romania | 42 participants |
| Region of Enrollment United Kingdom | 8 participants |
| Region of Enrollment United States | 12 participants |
| Sex: Female, Male Female | 62 Participants |
| Sex: Female, Male Male | 45 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 107 |
| other Total, other adverse events | 38 / 107 |
| serious Total, serious adverse events | 1 / 107 |
Outcome results
Primary
Adverse Drug Reactions (ADRs)
Number of Adverse Drug Reactions (ADRs)
Time frame: 8 weeks
Population: Safety analysis set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| LEO 80185 Gel | Adverse Drug Reactions (ADRs) | Blood cortisol decreased | 2 Number of adverse drug reactions |
| LEO 80185 Gel | Adverse Drug Reactions (ADRs) | Blood parathyroid hormone increased | 1 Number of adverse drug reactions |
| LEO 80185 Gel | Adverse Drug Reactions (ADRs) | Acne | 1 Number of adverse drug reactions |
| LEO 80185 Gel | Adverse Drug Reactions (ADRs) | Erythema | 1 Number of adverse drug reactions |
| LEO 80185 Gel | Adverse Drug Reactions (ADRs) | Hyperparathyroidism | 1 Number of adverse drug reactions |
| LEO 80185 Gel | Adverse Drug Reactions (ADRs) | Folliculitis | 1 Number of adverse drug reactions |
| LEO 80185 Gel | Adverse Drug Reactions (ADRs) | Headache | 1 Number of adverse drug reactions |
Primary
Change in 24-hour Urinary Calcium Excretion From Baseline to End of Treatment
Change in 24-hour urinary calcium excretion from baseline to end of treatment, defined as the last value recorded after baseline up to and including Week 8.
Time frame: From baseline to end of treatment
Population: Safety analysis set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LEO 80185 Gel | Change in 24-hour Urinary Calcium Excretion From Baseline to End of Treatment | 0.069 mmol/24hr | Standard Deviation 1.593 |
Primary
Change in 24-hour Urinary Calcium Excretion From Baseline to Week 4
Change in 24-hour urinary calcium excretion from baseline to Week 4
Time frame: From baseline to Week 4
Population: Safety analysis set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LEO 80185 Gel | Change in 24-hour Urinary Calcium Excretion From Baseline to Week 4 | -0.493 mmol/24hr | Standard Deviation 1.669 |
Primary
Change in 24-hour Urinary Calcium Excretion From Baseline to Week 8
Change in 24-hour urinary calcium excretion from baseline to Week 8
Time frame: From baseline to Week 8
Population: Safety analysis set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LEO 80185 Gel | Change in 24-hour Urinary Calcium Excretion From Baseline to Week 8 | 0.040 mmol/24hr | Standard Deviation 1.638 |
Primary
Change in Albumin-corrected Serum Calcium From Baseline to End of Treatment
Change in albumin-corrected serum calcium from baseline to end of treatment, defined as the last value recorded after baseline up to and including Week 8.
Time frame: From baseline to end of treatment
Population: Safety analysis set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LEO 80185 Gel | Change in Albumin-corrected Serum Calcium From Baseline to End of Treatment | -0.003 mmol/L | Standard Deviation 0.121 |
Primary
Change in Albumin-corrected Serum Calcium From Baseline to Week 4
Change in albumin-corrected serum calcium from baseline to Week 4
Time frame: From baseline to Week 4
Population: Safety analysis set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LEO 80185 Gel | Change in Albumin-corrected Serum Calcium From Baseline to Week 4 | -0.012 mmol/L | Standard Deviation 0.131 |
Primary
Change in Albumin-corrected Serum Calcium From Baseline to Week 8
Change in albumin-corrected serum calcium from baseline to Week 8
Time frame: From baseline to Week 8
Population: Safety analysis set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LEO 80185 Gel | Change in Albumin-corrected Serum Calcium From Baseline to Week 8 | -0.008 mmol/L | Standard Deviation 0.125 |
Primary
Subjects With Serum Cortisol Concentration of ≤18 mcg/dl at 30 Minutes After ACTH-challenge at Week 4
Number of subjects with serum cortisol concentration of ≤18 mcg/dl at 30 minutes after ACTH-challenge at Week 4
Time frame: 30 minutes after ACTH-challenge at Week 4
Population: Per protocol analysis set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| LEO 80185 Gel | Subjects With Serum Cortisol Concentration of ≤18 mcg/dl at 30 Minutes After ACTH-challenge at Week 4 | Serum cortisol equal to or below 18 mcg/dL | 4 Participants |
| LEO 80185 Gel | Subjects With Serum Cortisol Concentration of ≤18 mcg/dl at 30 Minutes After ACTH-challenge at Week 4 | Serum cortisol above 18 mcg/dL | 27 Participants |
Primary
Subjects With Serum Cortisol Concentration of ≤18 mcg/dl at 30 Minutes After ACTH-challenge at Week 8
Number of subjects with serum cortisol concentration of ≤18 mcg/dl at 30 minutes after ACTH-challenge at Week 8
Time frame: 30 minutes after ACTH-challenge at Week 8
Population: Per protocol analysis set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| LEO 80185 Gel | Subjects With Serum Cortisol Concentration of ≤18 mcg/dl at 30 Minutes After ACTH-challenge at Week 8 | Serum cortisol equal to or below 18 mcg/dL | 2 Participants |
| LEO 80185 Gel | Subjects With Serum Cortisol Concentration of ≤18 mcg/dl at 30 Minutes After ACTH-challenge at Week 8 | Serum cortisol above 18 mcg/dL | 27 Participants |
| LEO 80185 Gel | Subjects With Serum Cortisol Concentration of ≤18 mcg/dl at 30 Minutes After ACTH-challenge at Week 8 | No assessment performed | 2 Participants |
Secondary
Adverse Events (AEs)
Number of Adverse Events (AEs)
Time frame: 8 weeks
Population: Safety analysis set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| LEO 80185 Gel | Adverse Events (AEs) | Rhinitis | 2 Adverse Events |
| LEO 80185 Gel | Adverse Events (AEs) | Folliculitis | 1 Adverse Events |
| LEO 80185 Gel | Adverse Events (AEs) | Hordeolum | 1 Adverse Events |
| LEO 80185 Gel | Adverse Events (AEs) | Impetigo | 1 Adverse Events |
| LEO 80185 Gel | Adverse Events (AEs) | Peritonsillar abscess | 1 Adverse Events |
| LEO 80185 Gel | Adverse Events (AEs) | Upper respiratory tract infection | 1 Adverse Events |
| LEO 80185 Gel | Adverse Events (AEs) | Nasopharyngitis | 6 Adverse Events |
| LEO 80185 Gel | Adverse Events (AEs) | Viral infection | 1 Adverse Events |
| LEO 80185 Gel | Adverse Events (AEs) | Blood parathyroid hormone increased | 5 Adverse Events |
| LEO 80185 Gel | Adverse Events (AEs) | Blood cortisol decreased | 2 Adverse Events |
| LEO 80185 Gel | Adverse Events (AEs) | Eosinophil count increased | 1 Adverse Events |
| LEO 80185 Gel | Adverse Events (AEs) | Headache | 8 Adverse Events |
| LEO 80185 Gel | Adverse Events (AEs) | Balance disorder | 1 Adverse Events |
| LEO 80185 Gel | Adverse Events (AEs) | Dizziness | 1 Adverse Events |
| LEO 80185 Gel | Adverse Events (AEs) | Syncope | 1 Adverse Events |
| LEO 80185 Gel | Adverse Events (AEs) | Cough | 2 Adverse Events |
| LEO 80185 Gel | Adverse Events (AEs) | Oropharyngeal pain | 2 Adverse Events |
| LEO 80185 Gel | Adverse Events (AEs) | Dyspnoea | 1 Adverse Events |
| LEO 80185 Gel | Adverse Events (AEs) | Epistaxis | 1 Adverse Events |
| LEO 80185 Gel | Adverse Events (AEs) | Respiratory disorder | 1 Adverse Events |
| LEO 80185 Gel | Adverse Events (AEs) | Acne | 1 Adverse Events |
| LEO 80185 Gel | Adverse Events (AEs) | Erythema | 1 Adverse Events |
| LEO 80185 Gel | Adverse Events (AEs) | Pruritus | 1 Adverse Events |
| LEO 80185 Gel | Adverse Events (AEs) | Sunburn | 1 Adverse Events |
| LEO 80185 Gel | Adverse Events (AEs) | Abdominal pain upper | 1 Adverse Events |
| LEO 80185 Gel | Adverse Events (AEs) | Constipation | 1 Adverse Events |
| LEO 80185 Gel | Adverse Events (AEs) | Diarrhoea | 1 Adverse Events |
| LEO 80185 Gel | Adverse Events (AEs) | Back pain | 1 Adverse Events |
| LEO 80185 Gel | Adverse Events (AEs) | Muscle spasms | 1 Adverse Events |
| LEO 80185 Gel | Adverse Events (AEs) | Musculoskeletal chest pain | 1 Adverse Events |
| LEO 80185 Gel | Adverse Events (AEs) | Neck pain | 1 Adverse Events |
| LEO 80185 Gel | Adverse Events (AEs) | Dysmenorrhoea | 3 Adverse Events |
| LEO 80185 Gel | Adverse Events (AEs) | Arthropod sting | 1 Adverse Events |
| LEO 80185 Gel | Adverse Events (AEs) | Concussion | 1 Adverse Events |
| LEO 80185 Gel | Adverse Events (AEs) | Sleep disorder | 1 Adverse Events |
| LEO 80185 Gel | Adverse Events (AEs) | Suicide attempt | 1 Adverse Events |
| LEO 80185 Gel | Adverse Events (AEs) | Cardiovascular disorder | 1 Adverse Events |
| LEO 80185 Gel | Adverse Events (AEs) | Hyperparathyroidism | 1 Adverse Events |
| LEO 80185 Gel | Adverse Events (AEs) | Iron deficiency | 1 Adverse Events |
| LEO 80185 Gel | Adverse Events (AEs) | Wisdom teeth removal | 1 Adverse Events |
Secondary
Change in Serum Alkaline Phosphatase From Baseline to Week 4
Change in serum alkaline phosphatase from baseline to Week 4
Time frame: From baseline to Week 4
Population: Safety analysis set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LEO 80185 Gel | Change in Serum Alkaline Phosphatase From Baseline to Week 4 | -0.4 mmol/L | Standard Deviation 31.4 |
Secondary
Change in Serum Alkaline Phosphatase From Baseline to Week 8
Change in serum alkaline phosphatase from baseline to Week 8
Time frame: From baseline to Week 8
Population: Safety analysis set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LEO 80185 Gel | Change in Serum Alkaline Phosphatase From Baseline to Week 8 | -6.8 mmol/L | Standard Deviation 42.6 |
Secondary
Change in Urinary Calcium:Creatinine Ratio From Baseline to Week 4
Change in urinary calcium:creatinine ratio from baseline to Week 4
Time frame: From baseline to Week 4
Population: Safety analysis set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LEO 80185 Gel | Change in Urinary Calcium:Creatinine Ratio From Baseline to Week 4 | -0.098 mmol/g | Standard Deviation 1.642 |
Secondary
Change in Urinary Calcium:Creatinine Ratio From Baseline to Week 8
Change in urinary calcium:creatinine ratio from baseline to Week 8
Time frame: From baseline to Week 8
Population: Safety analysis set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LEO 80185 Gel | Change in Urinary Calcium:Creatinine Ratio From Baseline to Week 8 | 0.219 mmol/g | Standard Deviation 1.7 |
Secondary
Percentage Change in PASI From Baseline to End of Treatment
Percentage change in Psoriasis area and severity index (PASI) score from baseline to end of treatment, defined as the last value recorded up to and including Week 8. Psoriasis area and severity index (PASI) assesses extent and severity of clinical signs of psoriasis vulgaris. Body surface is divided in 4 ares: head (incl. neck), arms (incl. hands), trunk (incl. flexures) and legs (incl. buttocks and feet). Each area is scored from 0-6 for extent of psoriasis and from 0-4 for redness, thickness, and scaliness, and an area PASI score is calculated. The total PASI score is calculated from each area's score. The PASI score ranges from 0 (clear skin) to 72 (maximum disease), a PASI score higher than 10 generally corresponds to moderate-to-severe disease.
Time frame: From baseline to end of treatment
Population: Full analysis set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LEO 80185 Gel | Percentage Change in PASI From Baseline to End of Treatment | -78.7 Percentage change in PASI score | Standard Deviation 32.4 |
Secondary
Pharmacokinetic Evaluation AUC(0-infinity)
AUC(0-infinity) values for betamethasone dipropionate, betamethasone 17-propionate, calcipotriol, and MC1080. Betamethasone dipropionate was only detected above lower limit of quantification in 5 samples from 4 subjects, and no subjects had enough positive samples to allow calculation AUC(0-infinity) for betamethasone dipropionate. Betamethasone 17-propionate was only detected in 12 samples from 5 subjects, and only 2 subjects had enough positive samples to calculate AUC(0-infinity). The mean value of AUC(0-infinity) for these 2 subjects is presented for betamethasone 17-propionate. Calcipotriol and MC1080 were never detected above lower limit of quantification, therefore no PK parameters could be calculated and no data have been entered for calcipotriol and MC1080. The terms AUC(0-infinity) and AUC(all) are interchangeable, AUC(0-infinity) was used in the protocol whereas AUC(all) was used in the report. AUC(0-infinity) has been used here to be consistent with the protocol.
Time frame: Week 4, blood samples taken before IMP was applied and 1, 3, and 5 hours after application of IMP
Population: PK evaluation was performed in 32 subjects. Analysis set not defined in clinical trial protocol.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LEO 80185 Gel | Pharmacokinetic Evaluation AUC(0-infinity) | Betamethasone dipropionate | NA pg*h/mL | — |
| LEO 80185 Gel | Pharmacokinetic Evaluation AUC(0-infinity) | Betamethasone 17-propionate | 325 pg*h/mL | Standard Deviation 193.75 |
Secondary
Pharmacokinetic Evaluation AUC(0-t)
AUC(0-t) values for betamethasone dipropionate, betamethasone 17-propionate, calcipotriol, and MC1080. Betamethasone dipropionate was only detected above lower limit of quantification in 5 samples from 4 subjects, and no subjects had enough positive samples to allow calculation AUC(0-t) for betamethasone dipropionate. Betamethasone 17-propionate was only detected in 12 samples from 5 subjects, and only 2 subjects had enough positive samples to calculate AUC(0-t). The mean value of AUC(0-t) for these 2 subjects is presented for betamethasone 17-propionate. Calcipotriol and MC1080 were never detected above lower limit of quantification, therefore no PK parameters could be calculated and no data have been entered for calcipotriol and MC1080.
Time frame: Week 4, blood samples taken before IMP was applied and 1, 3, and 5 hours after application of IMP
Population: PK evaluation was performed in 32 subjects. Analysis set not defined in clinical trial protocol.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LEO 80185 Gel | Pharmacokinetic Evaluation AUC(0-t) | Betamethasone dipropionate | NA pg*h/mL | — |
| LEO 80185 Gel | Pharmacokinetic Evaluation AUC(0-t) | Betamethasone 17-propionate | 325 pg*h/mL | Standard Deviation 193.75 |
Secondary
Pharmacokinetic Evaluation C(Max)
C(max) values for betamethasone dipropionate, betamethasone 17-propionate, calcipotriol, and MC1080. Betamethasone dipropionate was only detected above lower limit of quantification in 5 samples from 4 subjects and betamethasone 17-propionate was only detected in 12 samples from 5 subjects, therefore pharmacokinetic profiles could not be calculated. Presented C(max) values for betamethasone dipropionate and betamethasone 17-propionate are the the single highest concentrations measured in any sample at any time. Calcipotriol and MC1080 were never detected above lower limit of quantification, therefore no PK parameters could be calculated and no data have been entered for calcipotriol and MC1080.
Time frame: Week 4, blood samples taken before IMP was applied and 1, 3, and 5 hours after application of IMP
Population: PK evaluation was performed in 32 subjects. Analysis set not defined in clinical trial protocol.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| LEO 80185 Gel | Pharmacokinetic Evaluation C(Max) | Betamethasone dipropionate | 104 pg/mL |
| LEO 80185 Gel | Pharmacokinetic Evaluation C(Max) | Betamethasone 17-propionate | 126 pg/mL |
Secondary
Pharmacokinetic Evaluation T(½)
T(½) values for betamethasone dipropionate, betamethasone 17-propionate, calcipotriol, and MC1080. Betamethasone dipropionate was only detected above lower limit of quantification in 5 samples from 4 subjects and betamethasone 17-propionate was only detected in 12 samples from 5 subjects, therefore it was not possible to calculate T(½) for betamethasone dipropionate or betamethasone 17-propionate. Calcipotriol and MC1080 were never detected above lower limit of quantification, therefore no PK parameters could be calculated and no data have been entered for calcipotriol and MC1080.
Time frame: Week 4, blood samples taken before IMP was applied and 1, 3, and 5 hours after application of IMP
Population: PK evaluation was performed in 32 subjects. Analysis set not defined in clinical trial protocol.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| LEO 80185 Gel | Pharmacokinetic Evaluation T(½) | Betamethasone dipropionate | NA h |
| LEO 80185 Gel | Pharmacokinetic Evaluation T(½) | Betamethasone 17-propionate | NA h |
Secondary
Pharmacokinetic Evaluation T(Max)
T(max) values for betamethasone dipropionate, betamethasone 17-propionate, calcipotriol, and MC1080. Betamethasone dipropionate was only detected above lower limit of quantification in 5 samples from 4 subjects and betamethasone 17-propionate was only detected in 12 samples from 5 subjects. Therefore it was not possible to calculate T(max) for betamethasone dipropionate and betamethasone 17-propionate. Calcipotriol and MC1080 were never detected above lower limit of quantification, therefore no PK parameters could be calculated and no data have been entered for calcipotriol and MC1080.
Time frame: Week 4, blood samples taken before IMP was applied and 1, 3, and 5 hours after application of IMP
Population: PK evaluation was performed in 32 subjects. Analysis set not defined in clinical trial protocol.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| LEO 80185 Gel | Pharmacokinetic Evaluation T(Max) | Betamethasone dipropionate | NA h |
| LEO 80185 Gel | Pharmacokinetic Evaluation T(Max) | Betamethasone 17-propionate | NA h |
Secondary
Subjects With Controlled Disease According to the Investigator's Global Assessment of Disease Severity on the Body at End of Treatment
Subjects with Controlled disease (i.e., Clear or Almost clear for subjects with at least Moderate disease at baseline, Clear for subjects with Mild disease at baseline) according to the investigator's global assessment of disease severity on the body at end of treatment, defined as the last value recorded up to and including Week 8.
Time frame: End of treatment
Population: Full analysis set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| LEO 80185 Gel | Subjects With Controlled Disease According to the Investigator's Global Assessment of Disease Severity on the Body at End of Treatment | Controlled | 62 Participants |
| LEO 80185 Gel | Subjects With Controlled Disease According to the Investigator's Global Assessment of Disease Severity on the Body at End of Treatment | Non-controlled | 45 Participants |
Secondary
Subjects With Controlled Disease According to the Patient's Global Assessment of Disease Severity on the Body at End of Treatment
Subjects with Controlled disease (i.e., Clear or Almost clear for subjects with at least Moderate disease at baseline, Clear for subjects with Mild disease at baseline) according to the patient's global assessment of disease severity on the body at end of treatment, defined as the last value recorded up to and including Week 8.
Time frame: End of treatment
Population: Full analysis set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| LEO 80185 Gel | Subjects With Controlled Disease According to the Patient's Global Assessment of Disease Severity on the Body at End of Treatment | Controlled | 67 Participants |
| LEO 80185 Gel | Subjects With Controlled Disease According to the Patient's Global Assessment of Disease Severity on the Body at End of Treatment | Non-controlled | 40 Participants |
Secondary
Subjects With Serum Cortisol Concentration of ≤18 mcg/dl at Both 30 and 60 Minutes After ACTH-challenge at Week 4
Number of subjects with serum cortisol concentration of ≤18 mcg/dl at both 30 and 60 minutes after ACTH-challenge at Week 4
Time frame: 30 and 60 minutes after ACTH-challenge at Week 4
Population: Per protocol analysis set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| LEO 80185 Gel | Subjects With Serum Cortisol Concentration of ≤18 mcg/dl at Both 30 and 60 Minutes After ACTH-challenge at Week 4 | Serum cortisol equal to or below 18 mcg/dL | 0 Participants |
| LEO 80185 Gel | Subjects With Serum Cortisol Concentration of ≤18 mcg/dl at Both 30 and 60 Minutes After ACTH-challenge at Week 4 | Serum cortisol above 18 mcg/dL | 31 Participants |
Secondary
Subjects With Serum Cortisol Concentration of ≤18 mcg/dl at Both 30 and 60 Minutes After ACTH-challenge at Week 8
Number of subjects with serum cortisol concentration of ≤18 mcg/dl at both 30 and 60 minutes after ACTH-challenge at Week 8
Time frame: 30 and 60 minutes after ACTH-challenge at Week 8
Population: Per protocol analysis set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| LEO 80185 Gel | Subjects With Serum Cortisol Concentration of ≤18 mcg/dl at Both 30 and 60 Minutes After ACTH-challenge at Week 8 | Serum cortisol equal to or below 18 mcg/dL | 0 Participants |
| LEO 80185 Gel | Subjects With Serum Cortisol Concentration of ≤18 mcg/dl at Both 30 and 60 Minutes After ACTH-challenge at Week 8 | Serum cortisol above 18 mcg/dL | 29 Participants |
| LEO 80185 Gel | Subjects With Serum Cortisol Concentration of ≤18 mcg/dl at Both 30 and 60 Minutes After ACTH-challenge at Week 8 | No assessment performed | 2 Participants |