A Phase 2 Maximal Use Systemic Exposure (MUSE) study evaluating the safety and efficacy of LEO 90100 used once daily in subjects with extensive psoriasis vulgaris.
The purpose of the present study is to assess the systemic safety of LEO 90100. Although LEO 90100 contains the same active ingredients in the same concentration as DAIVOBET/DOVOBET/TACLONEX ointment, the degree of absorption of the active ingredients from the new formulation may differ. Systemic safety will be assessed through the effect of LEO 90100 on calcium metabolism and HPA axis function under maximum use conditions (i.e., in subjects with very extensive psoriasis on the trunk, limbs and scalp, using up to 120g per week of LEO 90100 for up to 4 weeks). Data from this study, together with the measurements of albumin-corrected serum calcium and the calcium:creatinine ratio in spot urine samples in the planned phase 2 and 3 studies in the development program for LEO 90100, are expected to provide adequate information with respect to the systemic safety of LEO 90100.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
37
Calcipotriol 50 mcg/g (as hydrate) and betamethasone 0.5 mg/g (as dipropionate)
Guildford Dermatology Specialists
Surrey, British Columbia, Canada
PerCuro Clinical Research
Victoria, British Columbia, Canada
Winnipeg Clinic Dermatology Research
Winnipeg, Manitoba, Canada
Subjects With Serum Cortisol Concentration of ≤18 mcg/dl at 30 Minutes After Adrenocorticotrophic Hormone-challenge (ACTH-challenge)
HPA-axis testing by means of the rapid standard-dose cosyntropin test (ACTH-challenge test) for detection of adrenal suppression.
Time frame: Day 28
Change in Albumin-corrected Serum Calcium From Baseline to Day 28
The effect of LEO 90100 on calcium metabolism was evaluated based on change in albumin-corrected serum calcium from Baseline to Day 28.
Time frame: Baseline and Day 28
Change in 24-hour Urinary Calcium Excretion From Baseline to Day 28
The effect of LEO 90100 on calcium metabolism was evaluated based on change in 24-hour urinary calcium excretion from Baseline to Day 28 in 24-hour.
Time frame: Baseline and Day 28
Change in 24-hour Urinary Calcium:Creatinine Ratio From Baseline to Day 28
The effect of LEO 90100 on calcium metabolism was evaluated based on change in urinary calcium:creatinine ratio from Baseline to Day 28.
Time frame: Baseline and Day 28
Number of Subjects With Serum Cortisol Concentration of ≤18 mcg/dl at 30 and 60 Minutes After ACTH-challenge at Day 28
Serum cortisol concentrations at 30 and 60 minutes after injection were measured in order to assess the maximum stimulated cortisol level achieved. Potential adrenal suppression was indicated if the serum cortisol concentration is ≤18mcg/dl at 30 minutes after the injection.
Time frame: Day 28
Number of Participants With an Adverse Drug Reaction (ADR)
Adverse drug reactions (ADRs) were defined as adverse events for which the investigator has not described the causal relationship to investigational medication as "not related".
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Maritime Medical Research Center
Bathurst, New Brunswick, Canada
Ultranova Skincare
Barrie, Ontario, Canada
Co-Medica
Courtice, Ontario, Canada
Mediprobe Research
London, Ontario, Canada
The Centre for Dermatology
Richmond Hill, Ontario, Canada
K. Papp Clinical Research
Waterloo, Ontario, Canada
Centre de Dermatologie Maizerets
Québec, Quebec, Canada
Time frame: Baseline to Day 28
Change in Serum Phosphate From Baseline to Day 28
The effect of LEO 90100 on calcium metabolism was evaluated based on change in serum phosphate from Baseline to Day 28.
Time frame: Baseline and Day 28
Change in 24-hour Urinary Phosphate Excretion From Baseline to Day 28
The effect of LEO 90100 on calcium metabolism was evaluated based on change in 24-hour urinary phosphate excretion from Baseline to Day 28.
Time frame: Baseline and Day 28
Change in Urinary Phosphate: Creatinine Ratio From Baseline to Day 28
The effect of LEO 90100 on calcium metabolism was evaluated based on change in urinary phosphate:creatinine ratio from Baseline to Day 28.
Time frame: Baseline and Day 28
Change in Serum Alkaline Phosphatase (ALP) From Baseline to Day 28
The effect of LEO 90100 on calcium metabolism was evaluated based on change in serum ALP from Baseline to Day 28.
Time frame: Baseline and Day 28
Change in Plasma Parathyroid Hormone (PTH) From Baseline to Day 28
The effect of LEO 90100 on calcium metabolism was evaluated based on change in plasma PTH from Baseline to Day 28.
Time frame: Baseline and Day 28
Change in Blood Pressure From Baseline to Day 28
The effect of LEO 90100 on calcium metabolism was evaluated based on vital sign assessments (blood pressure).
Time frame: Baseline and Day 28
Change in Heart Rate From Baseline to Day 28
The effect of LEO 90100 on calcium metabolism was evaluated based on vital sign assessments (heart rate).
Time frame: Baseline and Day 28
Number of Subjects Who Discontinued From the Study
Number of subjects who discontinued from the study due to adverse events.
Time frame: Baseline to Day 28
Pharmacokinetic Evaluation Cmax
The following PK parameters will be calculated, if possible, for each assayed compound based on the obtained plasma concentrations: * AUC0-t * AUC0-∞ * Cmax * Tmax * T½ If it is not possible to calculate the above PK parameters, samples with plasma concentration above lower limit of quantification (LLOQ) will be presented. All subjects but 1 had plasma concentration of calcipotriol below the LLOQ (lower limit of quantification), and thus it was not possible to calculate group mean of the derived PK parameter based on one sample. Provided values for calcipotriol Cmax are derived from that 1 subject.
Time frame: 4 weeks / 28 days
Pharmacokinetic Evaluation AUClast
The following PK parameters will be calculated, if possible, for each assayed compound based on the obtained plasma concentrations: * AUC0-t * AUC0-∞ * Cmax * Tmax * T½ If it is not possible to calculate the above PK parameters, samples with plasma concentration above lower limit of quantification (LLOQ) will be presented. All subjects but 1 had plasma concentration of calcipotriol below the LLOQ (lower limit of quantification), and thus it was not possible to calculate group mean of the derived PK parameter based on one sample. Provided values for calcipotriol AUClast are derived from that 1 subject.
Time frame: 4 weeks / 28 days
Pharmacokinetic Evaluation AUCinf
The following PK parameters will be calculated, if possible, for each assayed compound based on the obtained plasma concentrations: * AUC0-t * AUC0-∞ * Cmax * Tmax * T½ If it is not possible to calculate the above PK parameters, samples with plasma concentration above lower limit of quantification (LLOQ) will be presented.
Time frame: 4 weeks / 28 days
Pharmacokinetic Evaluation Tmax
The following PK parameters will be calculated, if possible, for each assayed compound based on the obtained plasma concentrations: * AUC0-t * AUC0-∞ * Cmax * Tmax * T½ If it is not possible to calculate the above PK parameters, samples with plasma concentration above lower limit of quantification (LLOQ) will be presented. All subjects but 1 had plasma concentration of calcipotriol below the LLOQ (lower limit of quantification), and thus it was not possible to calculate group mean of the derived PK parameter based on one sample. Provided values for calcipotriol Tmax are derived from that 1 subject.
Time frame: 4 weeks / 28 days
Pharmacokinetic Evaluation T1/2
The following PK parameters will be calculated, if possible, for each assayed compound based on the obtained plasma concentrations: * AUC0-t * AUC0-∞ * Cmax * Tmax * T½ If it is not possible to calculate the above PK parameters, samples with plasma concentration above lower limit of quantification (LLOQ) will be presented.
Time frame: 4 weeks / 28 days
Efficacy Evaluation
The percentage of subjects who achieved 'controlled disease' (i.e., Clear or Almost clear) according to the Investigator's Global Assessment (IGA) of disease severity on the trunk, limbs and scalp at Days 28 (Visit 3) and End of treatment (EoT) were presented.
Time frame: 4 weeks I 28 days and End of treatment