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Effect of LEO 90100 on the HPA Axis and Calcium Metabolism in Subjects With Extensive Psoriasis VulgarisExtensive Psoriasis Vulgaris

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ClinicalTrials.gov Identifier: NCT01600222
Recruitment Status : Completed
First Posted : May 17, 2012
Results First Posted : September 16, 2016
Last Update Posted : September 16, 2016
Sponsor:
Information provided by (Responsible Party):
LEO Pharma

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Psoriasis Vulgaris Drug: LEO 90100 Phase 2

Detailed Description:
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  (Clinical Trial)
Actual Enrollment : 37 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Study Start Date : May 2012
Actual Primary Completion Date : May 2013
Actual Study Completion Date : May 2013

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Psoriasis

Arm Intervention/treatment
Experimental: LEO 90100 Drug: LEO 90100
Calcipotriol 50 mcg/g (as hydrate) and betamethasone 0.5 mg/g (as dipropionate)




Primary Outcome Measures :
  1. Subjects With Serum Cortisol Concentration of ≤18 mcg/dl at 30 Minutes After Adrenocorticotrophic Hormone-challenge (ACTH-challenge) [ Time Frame: Day 28 ]
    HPA-axis testing by means of the rapid standard-dose cosyntropin test (ACTH-challenge test) for detection of adrenal suppression.

  2. Change in Albumin-corrected Serum Calcium From Baseline to Day 28 [ Time Frame: Baseline and 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.

  3. Change in 24-hour Urinary Calcium Excretion From Baseline to Day 28 [ Time Frame: Baseline and 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.

  4. Change in 24-hour Urinary Calcium:Creatinine Ratio From Baseline to Day 28 [ Time Frame: Baseline and 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.


Secondary Outcome Measures :
  1. Number of Subjects With Serum Cortisol Concentration of ≤18 mcg/dl at 30 and 60 Minutes After ACTH-challenge at Day 28 [ Time Frame: 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.

  2. Number of Participants With an Adverse Drug Reaction (ADR) [ Time Frame: Baseline to Day 28 ]
    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".

  3. Change in Serum Phosphate From Baseline to Day 28 [ Time Frame: Baseline and Day 28 ]
    The effect of LEO 90100 on calcium metabolism was evaluated based on change in serum phosphate from Baseline to Day 28.

  4. Change in 24-hour Urinary Phosphate Excretion From Baseline to Day 28 [ Time Frame: Baseline and 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.

  5. Change in Urinary Phosphate: Creatinine Ratio From Baseline to Day 28 [ Time Frame: Baseline and 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.

  6. Change in Serum Alkaline Phosphatase (ALP) From Baseline to Day 28 [ Time Frame: Baseline and Day 28 ]
    The effect of LEO 90100 on calcium metabolism was evaluated based on change in serum ALP from Baseline to Day 28.

  7. Change in Plasma Parathyroid Hormone (PTH) From Baseline to Day 28 [ Time Frame: Baseline and Day 28 ]
    The effect of LEO 90100 on calcium metabolism was evaluated based on change in plasma PTH from Baseline to Day 28.

  8. Change in Blood Pressure From Baseline to Day 28 [ Time Frame: Baseline and Day 28 ]
    The effect of LEO 90100 on calcium metabolism was evaluated based on vital sign assessments (blood pressure).

  9. Change in Heart Rate From Baseline to Day 28 [ Time Frame: Baseline and Day 28 ]
    The effect of LEO 90100 on calcium metabolism was evaluated based on vital sign assessments (heart rate).

  10. Number of Subjects Who Discontinued From the Study [ Time Frame: Baseline to Day 28 ]
    Number of subjects who discontinued from the study due to adverse events.

  11. Pharmacokinetic Evaluation Cmax [ Time Frame: 4 weeks / 28 days ]

    The following PK parameters will be calculated, if possible, for each assayed compound based on the obtained plasma concentrations:

    • AUC0-t
    • AUC0-∞
    • Cmax
    • Tmax

    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.


  12. Pharmacokinetic Evaluation AUClast [ Time Frame: 4 weeks / 28 days ]

    The following PK parameters will be calculated, if possible, for each assayed compound based on the obtained plasma concentrations:

    • AUC0-t
    • AUC0-∞
    • Cmax
    • Tmax

    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.


  13. Pharmacokinetic Evaluation AUCinf [ Time Frame: 4 weeks / 28 days ]

    The following PK parameters will be calculated, if possible, for each assayed compound based on the obtained plasma concentrations:

    • AUC0-t
    • AUC0-∞
    • Cmax
    • Tmax

    If it is not possible to calculate the above PK parameters, samples with plasma concentration above lower limit of quantification (LLOQ) will be presented.


  14. Pharmacokinetic Evaluation Tmax [ Time Frame: 4 weeks / 28 days ]

    The following PK parameters will be calculated, if possible, for each assayed compound based on the obtained plasma concentrations:

    • AUC0-t
    • AUC0-∞
    • Cmax
    • Tmax

    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.


  15. Pharmacokinetic Evaluation T1/2 [ Time Frame: 4 weeks / 28 days ]

    The following PK parameters will be calculated, if possible, for each assayed compound based on the obtained plasma concentrations:

    • AUC0-t
    • AUC0-∞
    • Cmax
    • Tmax

    If it is not possible to calculate the above PK parameters, samples with plasma concentration above lower limit of quantification (LLOQ) will be presented.


  16. Efficacy Evaluation [ Time Frame: 4 weeks I 28 days and End of treatment ]
    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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Signed and dated informed consent obtained prior to any trial related activities (including any washout period)
  • Age 18 years or above
  • Either sex
  • Any race or ethnicity
  • Any skin type
  • Attending a hospital out-patient clinic or the private practice of a dermatologist for treatment of psoriasis vulgaris
  • At SV2 and Day 0 (Visit 1), a clinical diagnosis of psoriasis vulgaris of at least 6 months duration involving the trunk and/or limbs and the scalp which is;

    • amenable to topical treatment with a maximum of 120g of study medication per week
    • of an extent of between 15 and 30% of the body surface area (BSA) excluding psoriatic lesions of the face, genitals and skin folds
    • including at least 30% scalp involvement
    • of at least a moderate disease severity according to the investigators global assessment (IGA)
  • At SV2, a normal HPA axis function including a serum cortisol concentration above 5 mcg/dl before ACTH-challenge and above 18 mcg/dl 30 minutes after ACTH-challenge
  • At SV2, an albumin-corrected serum calcium below the upper reference range limit
  • At SV2, females of child-bearing potential must have a negative urine pregnancy result
  • Females of child-bearing potential must agree to use a highly effective method of contraception during the study. A highly effective method of birth control is defined as one which results in a low failure rate (less than 1% per year)
  • Able to communicate with the investigator and understand and comply with the requirements of the study

Exclusion Criteria:

  • A history of allergic asthma, serious allergy or serious allergic skin rash
  • Known or suspected hypersensitivity to component(s) of LEO 90100 or CORTROSYN (including cosyntropin/tetracosactide)
  • Systemic treatment with corticosteroids (including inhaled and nasal steroids) within 12 weeks prior to SV2
  • Systemic treatment with biological therapies (whether marketed or not marketed), with a possible effect on psoriasis vulgaris within the following time period prior to Day 0 (Visit 1);

    • etanercept - within 4 weeks
    • adalimumab, alefacept, infliximab - within 8 weeks
    • ustekinumab - within 16 weeks
    • other products - within 4 weeks/5 half-lives (whichever is longer)
  • Subjects who have received treatment with any non-marketed drug substance (i.e. a drug which has not yet been made available for clinical use following registration) within 4 weeks/5 half-lives (whichever is longer) prior to Day 0 (Visit 1)
  • Systemic treatment with all other therapies with a possible effect on psoriasis vulgaris (e.g. retinoids, methotrexate, cyclosporine and other immunosuppressants) within 4 weeks prior to Day 0 (Visit 1)
  • PUVA therapy within 4 weeks prior to Day 0 (Visit 1)
  • UVB therapy within 2 weeks prior to day 0 (Visit 1).
  • Topical treatment with corticosteroids or vitamin D analogues on any body location within 2 weeks prior to SV2
  • Any topical treatment of psoriasis vulgaris on the trunk, limbs or scalp (except for emollients and non-medicated shampoos) within 2 weeks prior to Day 0 (Visit 1)
  • Planned initiation of, or changes to, concomitant medication that could affect psoriasis vulgaris (e.g., betablockers, antimalarials, lithium, ACE inhibitors) during the study
  • Oral calcium supplements, vitamin D supplements, bisphosphonates or calcitonin within 4 weeks prior to SV2. Note: Stable doses of oral vitamin D supplementation ≤400 IU/day is permitted provided there are no dose adjustments during the study period
  • Planned initiation of, or changes to concomitant medication that could affect calcium metabolism (e.g. antacids, thiazide and/or loop diuretics, antiepileptics) during the study
  • Planned excessive exposure of area(s) to be treated with study medication to either natural or artificial sunlight (including tanning booths, sunlamps etc.) during the study
  • Oestrogen therapy (including contraceptives), antidepressant medications and any other medication known to affect cortisol levels or HPA axis integrity within 4 weeks prior to SV2
  • Cytochrome P450 3A4 (CYP 3A4) inducers (e.g., barbiturates, phenytoin, rifampicin) within 4 weeks prior to SV2
  • Systemic cytochrome P450 3A4 (CYP 3A4) inhibitors (e.g., ketoconazole, itraconazole, metronidazole) within 4 weeks prior to SV2
  • Topical cytochrome P450 3A4 (CYP 3A4) inhibitors (e.g., ketoconazole) within 2 weeks prior to SV2
  • Non-nocturnal sleep patterns (e.g. night shift workers)
  • Any of the following conditions, whether known or suspected:

    • depression and endocrine disorders (e.g. Cushing's disease, Addison's disease, diabetes mellitus) known to affect cortisol levels or HPA axis integrity
    • disorders of calcium metabolism associated with hypercalcaemia
    • cardiac disorders associated with abnormal QT intervals or rhythm disturbances including clinically significant bradycardia or tachycardia
    • severe renal insufficiency
    • severe hepatic disorders
  • Any clinically significant abnormality following blood pressure/heart rate measurement or review of screening laboratory tests (blood and spot urine samples) collected at SV2
  • Any clinically significant abnormality following physical examination at SV1
  • Current diagnosis of guttate, erythrodermic, exfoliative or pustular psoriasis
  • Any of the following conditions present on the study treatment areas (trunk, limbs and scalp): 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, acne vulgaris, atrophic skin, striae atrophicae, fragility of skin veins, ichthyosis, ulcers and wounds
  • Other inflammatory skin disorders (e.g. seborrhoeic dermatitis and contact dermatitis) that may confound the evaluation of psoriasis vulgaris
  • Current participation in any other interventional clinical trial
  • Previously enrolled in this trial
  • Known or suspected of not being able to comply with the trial protocol (e.g., alcoholism, drug dependency or psychotic state)
  • Females who are pregnant, wishing to become pregnant during the study or who are breast-feeding

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01600222


Locations
Canada, British Columbia
Guildford Dermatology Specialists
Surrey, British Columbia, Canada, V3R 6A7
PerCuro Clinical Research
Victoria, British Columbia, Canada, V8V 3P9
Canada, Manitoba
Winnipeg Clinic Dermatology Research
Winnipeg, Manitoba, Canada, R3C 0N2
Canada, New Brunswick
Maritime Medical Research Center
Bathurst, New Brunswick, Canada, E2A 4Z9
Canada, Ontario
Ultranova Skincare
Barrie, Ontario, Canada, L4M 6L2
Co-Medica
Courtice, Ontario, Canada, L1E 3C3
Mediprobe Research
London, Ontario, Canada, N5X 2P1
The Centre for Dermatology
Richmond Hill, Ontario, Canada, L4B 1A5
K. Papp Clinical Research
Waterloo, Ontario, Canada, N2J 1C4
Canada, Quebec
Centre de Dermatologie Maizerets
Quebec City, Quebec, Canada, G1J 1X7
Sponsors and Collaborators
LEO Pharma
Investigators
Principal Investigator: Vicki Taraska Winnipeg Clinic

Additional Information:
Publications of Results:
Taraska V, Tuppal R, Olesen M, Bang Pedersen C, Papp K. Fixed combination aerosol foam calcipotriene (Cal) 0.005% plus betamethasone 0.064% (as dipropionate; BD) exhibits no impact on the HPA axis and calcium homeostasis in patients with extensive psoriasis vulgaris: a multicenter, single-arm, Phase II, 4-week MUSE study. Semin Cutan Med Surg. 2015;34 S1:PA-29.
Taraska V, Tuppal R, Olesen M, Bang Pedersen C, Papp K. Fixed combination aerosol foam calcipotriene 0.005% (Cal) plus betamethasone dipropionate 0.064% (BD) exhibits no impact on the HPA axis and calcium homeostasis in patients with extensive psoriasis vulgaris: a multicenter, single-arm, Phase II, 4-week MUSE study. Semin Cutan Med Surg 2014;33:abst PA-13.

Responsible Party: LEO Pharma
ClinicalTrials.gov Identifier: NCT01600222     History of Changes
Other Study ID Numbers: LEO 90100-30
First Posted: May 17, 2012    Key Record Dates
Results First Posted: September 16, 2016
Last Update Posted: September 16, 2016
Last Verified: July 2016

Additional relevant MeSH terms:
Psoriasis
Skin Diseases, Papulosquamous
Skin Diseases