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Effect of LEO 80185 Gel on the HPA Axis and Calcium Metabolism in Subjects With Extensive Psoriasis Vulgaris

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
LEO Pharma
ClinicalTrials.gov Identifier:
NCT01229098
First received: October 26, 2010
Last updated: October 25, 2013
Last verified: July 2011
  Purpose

The purpose of this study is to evaluate the effect of once daily use of LEO 80185 gel on the hypothalamic-pituitary-adrenal (HPA) axis and calcium metabolism in subjects with extensive psoriasis vulgaris.


Condition Intervention Phase
Psoriasis Vulgaris
Drug: LEO 80185 (Xamiol® gel/Taclonex® Scalp topical suspension)
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2 Maximal Use Systemic Exposure Study Evaluating the Safety and Efficacy of Calcipotriol 50 Mcg/g Plus Betamethasone 0.5 mg/g (as Dipropionate) Gel Applied Once Daily in Subjects With Extensive Psoriasis Vulgaris on the Scalp and Non-scalp Regions of the Body (Trunk and/or Limbs)

Resource links provided by NLM:


Further study details as provided by LEO Pharma:

Primary Outcome Measures:
  • Safety [ Time Frame: Up to 8 weeks ] [ Designated as safety issue: Yes ]
    • Subjects with serum cortisol concentration of ≤18 mcg/dl at 30 minutes after ACTH-challenge [ Time Frame: Week 4 and week 8 ] [ Designated as safety issue: Yes ]
    • Change in albumin-corrected serum calcium from baseline [ Time Frame: Week 4 and week 8 ] [ Designated as safety issue: Yes ]
    • Change in 24-hour urinary calcium excretion from baseline [ Time Frame: Week 4 and week 8 ] [ Designated as safety issue: Yes ]
    • Change in urinary calcium:creatinine ratio from baseline [ Time Frame: Week 4 and week 8 ] [ Designated as safety issue: Yes ]


Secondary Outcome Measures:
  • Efficacy [ Time Frame: Up to 8 weeks ] [ Designated as safety issue: No ]
    • Subjects with "Controlled disease" (i.e., "Clear" or "Almost clear") according to the investigator's global assessment of disease severity [ Time Frame: Weeks 2, 4, 8 ] [ Designated as safety issue: No ]
    • Pharmacokinetic parameters for calcipotriol, betamethasone dipropionate and any metabolites.


Enrollment: 102
Study Start Date: October 2010
Study Completion Date: October 2011
Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: LEO 80185 Drug: LEO 80185 (Xamiol® gel/Taclonex® Scalp topical suspension)
LEO 80185 (Taclonex® Scalp topical suspension/Xamiol® gel) Topical suspension applied once daily for up to 8 weeks

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Signed and dated informed consent obtained following receipt of verbal and written information about the study prior to any trial related activities (including any wash-out period).
  2. Age 18 years or above.
  3. Either sex.
  4. Any race or ethnicity.
  5. Attending a hospital out-subject clinic or the private practice of a dermatologist for treatment of psoriasis vulgaris.
  6. Clinical diagnosis of psoriasis vulgaris involving non scalp regions of the body (trunk and/or limbs) with or without involvement of the scalp.
  7. At SV2 and Day 0 (Visit 1) a clinical diagnosis of psoriasis vulgaris which is:

    • amenable to topical treatment with a maximum of 100 g of study medication per week, and
    • of an extent of between 15 and 30% of the body surface area (BSA) excluding psoriasis on the face, genitals or skin folds.
    • a disease severity on the trunk and/or limbs graded as at least moderate according to the investigator's global assessment (IGA)
  8. Subjects with normal HPA axis function at SV2 including a serum cortisol concentration above 5 mcg/dL before ACTH challenge test and above 18 mcg/dL 30 minutes after ACTH challenge test.
  9. Albumin-corrected serum calcium, below the upper reference limit at SV2.
  10. Females of child-bearing potential must have a negative urine pregnancy test result at baseline Visit SV2 and must agree to use a highly effective method of contraception during the study. Highly effective methods are defined as ones which results in a low failure rate (less than 1% per year) such as progestin-only formulations (implants, injectables), some intra-uterine devices, or vasectomised partner. Subjects must have used the contraceptive method continuously for at least 1 month prior to the pregnancy test and must continue using the contraceptive method for at least 1 week after the last application of study medication (or until study visit FU2 if applicable). A female is defined as not of child-bearing potential if she is postmenopausal (12 months with no menses without an alternative medical cause), or surgically sterile (tubal ligation/section, hysterectomy or bilateral ovariectomy).
  11. Able to communicate with the investigator and understand and comply with the requirements of the study.

    Exclusion Criteria:

  12. A history of serious allergy, allergic asthma or serious allergic skin rash
  13. Known or suspected hypersensitivity to any medication (including ACTH/cosyntropin/tetracosactide) or to any component of the LEO 80185 gel or CORTROSYN.
  14. Systemic treatment with corticosteroids (including inhaled and nasal steroids) within 12 weeks prior to SV2 and during the study.
  15. Systemic treatment with biological therapies (marketed or not marketed), with a possible effect on psoriasis vulgaris within the following time period prior to Day 0 (Visit 1) and during the study:

    • etanercept - within 4 weeks prior to Visit 1
    • adalimumab, alefacept, infliximab -within 2 months prior to Visit 1
    • ustekinumab, briakinumab - within 4 months prior to Visit 1
    • experimental products - within 4 weeks/5 half-lives (whichever is longer) prior to Visit 1
  16. Systemic treatment with therapies other than biologicals, with a possible effect on psoriasis vulgaris (e.g., retinoids, methotrexate, immunosuppressants) within 4 weeks prior to Visit 1 (Day 0) or during the study.
  17. PUVA or Grenz ray therapy within 4 weeks prior to Visit 1 (Day 0) or during the study
  18. UVB therapy within 2 weeks prior to Visit 1 (Day 0) or during the study.
  19. Topical treatment with corticosteroids or vitamin D analogues (calcipotriol, calcitriol or tacalcitol) on any body location within 2 weeks prior to SV2 or during the study.
  20. Any topical treatment of psoriasis vulgaris on the scalp or trunk and/or limbs (except for emollients and non-steroid medicated shampoos) within 2 weeks prior to Visit 1 (Day 0) or during the study.
  21. Oral calcium supplements, vitamin D supplements, antacids, thiazide and/or loop diuretics, antiepileptics, diphosphonates or calcitonin within 4 weeks prior to SV2 and during the study. Note: Stable doses of oral vitamin D supplementation ≤400 IU/day is permitted provided there are no dose adjustments during the study period.
  22. Planned initiation of, or changes to, concomitant medication that could affect psoriasis vulgaris (e.g., betablockers, antimalarials, lithium, ACE inhibitors) during the study.
  23. Planned excessive exposure of treated areas to either natural or artificial sunlight (e.g. sunlamps etc.) during the study that may affect the psoriasis vulgaris.
  24. Oestrogen therapy (including contraceptives) or any other medication known to affect cortisol levels or HPA axis integrity within 4 weeks prior to SV2 or during the study.
  25. Cytochrome P450 3A4 (CYP 3A4) inducers (e.g., barbiturates, phenytoin, rifampicin) within 4 weeks prior to SV2 or during the study.
  26. Systemic or topical cytochrome P450 3A4 (CYP 3A4) inhibitors (e.g., ketoconazole, itraconazole, metronidazole) within 4 weeks prior to SV2 or during the study. Topical ketoconazole within 2 weeks prior to SV2.
  27. Hypoglycaemic sulfonamides within 4 weeks prior to the SV2 or during the study.
  28. Antidepressant medications within 4 weeks prior to SV2 or during the study.
  29. Not following nocturnal sleep patterns (e.g. night shift workers are excluded).
  30. Known or suspected endocrine disorder that may affect the results of the ACTH challenge test.
  31. Clinical signs or symptoms of Cushing's disease or Addison's disease.
  32. Known or suspected diabetes mellitus.
  33. Known or suspected cardiac disorders associated with abnormal QT intervals or rhythm disturbances including clinically significant bradycardia or tachycardia.
  34. Known or suspected severe renal insufficiency or severe hepatic disorders.
  35. Known or suspected disorders of calcium metabolism associated with hypercalcaemia.
  36. Any clinically significant abnormality following review of screening laboratory tests (blood and spot urine samples), physical examination or blood pressure/heart rate measurement performed at SV2.
  37. Current diagnosis of guttate, erythrodermic, exfoliative or pustular psoriasis.
  38. Any of the following conditions present on the study treatment areas: 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.
  39. Other inflammatory skin diseases that may confound the evaluation of psoriasis vulgaris (e.g. seborrhoeic dermatitis, contact dermatitis and cutaneous mycosis).
  40. Current participation in any other interventional clinical trial.
  41. Previously enrolled in this trial (with the exception of subjects excluded due to hypocalcaemia prior to implementation of Consolidated Clinical Study Protocol 2).
  42. Received any non-marketed drug substance (i.e., an agent which has not yet been made available for clinical use following registration) within 4 weeks or 5 half-lives (whichever is longer) prior to SV1.
  43. Known or suspected of not being able to comply with the trial protocol (e.g., alcoholism, drug dependency or psychotic state).
  44. Females who are pregnant, have a positive urine pregnancy test at baseline Visit SV2, or are breast-feeding. Females of child-bearing potential and wishing to become pregnant during the study or not using an adequate method of contraception during the study.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01229098

Locations
Canada, Manitoba
Dermadvances Research
Winnipeg, Manitoba, Canada, R3C 1R4
Winnipeg Clinic
Winnipeg, Manitoba, Canada, R3C 0N2
Canada, Newfoundland and Labrador
Alpha Clinical Research Centre
Saint John's, Newfoundland and Labrador, Canada, A1B 4S8
Newlab Clinical Research
St. John's, Newfoundland and Labrador, Canada, A1C 2H5
Canada, Nova Scotia
Eastern Canada Cutaneous Research Associates Ltd.
Halifax, Nova Scotia, Canada, B3H 1Z4
Canada, Ontario
Dermsearch
London, Ontario, Canada, N5X 2P1
Lynderm Research Inc.
Markham, Ontario, Canada, L3P 1A8
Institute of Cosmetic and Laser Surgery
Oakville, Ontario, Canada, L6J 7W5
Co-Medica Research Network Inc.
Oshawa, Ontario, Canada, L1E 3C3
Oshawa Clinic
Oshawa, Ontario, Canada, L1H 1B9
Sponsors and Collaborators
LEO Pharma
Investigators
Principal Investigator: Shane Silver, MB Dermadvances Research, 203 Edmonton Street, Winnipeg, Manitoba R3C 1R4 Canada
  More Information

No publications provided by LEO Pharma

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: LEO Pharma
ClinicalTrials.gov Identifier: NCT01229098     History of Changes
Other Study ID Numbers: LEO 80185-G24
Study First Received: October 26, 2010
Last Updated: October 25, 2013
Health Authority: Canada: Health Canada

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

ClinicalTrials.gov processed this record on November 20, 2014