An International, Multi-centre, Prospective, Non-controlled, Open, Single-group, 8-week Trial in Adolescent Subjects

Effect of Calcipotriol Plus Betamethasone Dipropionate Gel on the HPA Axis and Calcium Metabolism in Adolescent Subjects (Aged 12 to 16 Years, 11 Months) With Scalp and Body Psoriasis

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.

Study Overview

• Status: Completed
• Conditions: Psoriasis Vulgaris
• Intervention / Treatment: Drug: LEO 80185 gel

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.

• Study Type: Interventional
• Enrollment (Actual): 125
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3C 0N2
      • Winnipeg Clinic
  • Newfoundland and Labrador
    • St-John's, Newfoundland and Labrador, Canada, A1A 4Y3
      • Adult, Pediatric and Laser Derma
  • Ontario
    • Markham, Ontario, Canada, L3P 1A8
      • Lynderm Research Inc.
    • Peterborough, Ontario, Canada, K9J 1Z2
      • Skin Centre for Dermatology
• France
  • Alpe-Maritimes
    • Nice, Alpe-Maritimes, France, 06202
      • CHU de Nice
  • Bouches-du-Rhône
    • Martigues, Bouches-du-Rhône, France, 13500
      • Cabinet Medical
  • Finistère
    • Quimper, Finistère, France, 29107
      • CHI de Cornouaille
• Germany
  • Berlin, Germany, 10117
    • Charite Berlin
  • Bonn, Germany, 53127
    • Uniklinik Bonn
  • Frankfurt am Main, Germany, 60590
    • Uniklinik Frankfurt
  • Hamburg, Germany, 22149
    • Katholisches Kinderkrankenhaus
• Poland
  • Karczew, Poland, 05-480
    • Endo - Med. Centrum Medyczne Clinic
  • Lublin, Poland, 20-146
    • NZOZ Med.-Laser Clinic
  • Ostróda, Poland, 14-100
    • Specjalistyczny Ofrodek Leczniczo Clinic
  • Warszawa, Poland, 00-660
    • Medycyna Kliniczna Clinic
  • Wrocław, Poland, 51-318
    • Derm Medica Sp.zo.o. Clinic
• Romania
  • Brasov, Romania, 500152
    • Policlinica de Diagnostic Rapid S.A. Clinic
  • Bucharest, Romania, 20125
    • Spitalul Clinic "Colentina"
  • Cluj-Napoca, Romania, 400006
    • Spitalul Clinic Judetean de Urgenta Cluj-Napoca
  • Galati, Romania, 800101
    • Cabinet Medical Individual Tatu G. Alin Laurentiu
  • Iasi, Romania, 700381
    • Iasiprest SRL Dermato-Venerology
  • Targu-Mures, Romania, 800373
    • Spitalul Clinic Judetean Mures
  • Timisoara, Romania, 300077
    • Spitalul Clinic Municipal de Urgenta Timisoara
• United Kingdom
  • Greater Manchester
    • Manchester, Greater Manchester, United Kingdom, M13 9WL
      • Manchester Royal Infirmary
  • Lanarkshire
    • Airdrie, Lanarkshire, United Kingdom, ML6 OJ5
      • Monklands Hospital
  • London
    • Leytonstone, London, United Kingdom, E11 1NR
      • Whipps Cross University Hospital
  • Monmouthshire
    • Stow Hill, Newport, Monmouthshire, United Kingdom, NP20 4SZ
      • St. Woolos Hospital
• United States
  • California
    • San Diego, California, United States, 92132
      • Rady's Children Hospital
  • Florida
    • Tampa, Florida, United States, 33612
      • Clinical Research Center, Morsani Center for Advanced Healthcare
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University
  • Nebraska
    • Omaha, Nebraska, United States, 68144
      • Skin Specialists, PC
  • New York
    • Forest Hills, New York, United States, 10025
      • St. Luke's Roosevelt Hospital
  • Rhode Island
    • Johnston, Rhode Island, United States, 12095
      • Clinical Partners
  • South Carolina
    • Charleston, South Carolina, United States, 29407
      • Dermatology and Laser Center of Charleston, PA
  • Texas
    • San Antonio, Texas, United States, 78229
      • Clinical Trials of Texas, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 17 years (Child)
• Accepts Healthy Volunteers: No

Description

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.

Exclusion Criteria (for subjects performing HPA axis assessments)

• A history of serious allergy, allergic asthma or serious allergic skin rash.
• Known or suspected hypersensitivity to any component of CORTROSYN® (including ACTH/cosyntropin/tetracosactide)
• Systemic treatment with corticosteroids (including inhaled and nasal steroids) within 12 weeks prior to SV2 or during the trial.
• Topical treatment with corticosteroids within 2 weeks prior to SV2 or during the trial.
• Oestrogen therapy (including contraceptives) or any other medication known to affect cortisol levels levels or HPA axis integrity within 4 weeks prior to SV2 or during the trial.
• Enzymatic inductors (e.g., barbiturates, phenytoin, rifampicin) within 4 weeks prior to SV2 or during the trial.
• Systemic or topical cytochrome P450 inhibitors (e.g., ketoconazole, itraconazole, metronidazole) within 4 weeks prior to SV2 or during the trial. Topical ketoconazole 2 weeks prior to SV2.
• Hypoglycemic sulfonamides within 4 weeks prior to SV2 or during the trial.
• Antidepressive medications within 4 weeks prior to SV2 or during the trial.
• Known or suspected endocrine disorder that may affect the results of the ACTH challenge test.
• Clinical signs or symptoms of Cushing's disease or Addison's disease.
• Subjects with diabetes mellitus.
• Known or suspected cardiac condition.
• Not following nocturnal sleep patterns.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LEO 80185 gel	Drug: LEO 80185 gel

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Drug Reactions (ADRs)	Number of Adverse Drug Reactions (ADRs)	8 weeks
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	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	Number of 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
Change in Albumin-corrected Serum Calcium From Baseline to Week 4	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 8	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 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.	From baseline to end of treatment
Change in 24-hour Urinary Calcium Excretion From Baseline to Week 4	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 8	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 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.	From baseline to end of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events (AEs)	Number of Adverse Events (AEs)	8 weeks
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	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	Number of 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
Change in Urinary Calcium:Creatinine Ratio From Baseline to Week 4	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 8	Change in urinary calcium:creatinine ratio from baseline to Week 8	From baseline to Week 8
Change in Serum Alkaline Phosphatase From Baseline to Week 4	Change in serum alkaline phosphatase from baseline to Week 4	From baseline to Week 4
Change in Serum Alkaline Phosphatase From Baseline to Week 8	Change in serum alkaline phosphatase from baseline to Week 8	From baseline to Week 8
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.	Week 4, blood samples taken before IMP was applied and 1, 3, and 5 hours after application of IMP
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.	Week 4, blood samples taken before IMP was applied and 1, 3, and 5 hours after application of IMP
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.	Week 4, blood samples taken before IMP was applied and 1, 3, and 5 hours after application of IMP
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.	Week 4, blood samples taken before IMP was applied and 1, 3, and 5 hours after application of IMP
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.	Week 4, blood samples taken before IMP was applied and 1, 3, and 5 hours after application of IMP
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.	End of treatment
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.	From baseline to end of treatment
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.	End of treatment

Collaborators and Investigators

• Sponsor: LEO Pharma
• Investigators: Principal Investigator: Lawrence Eichenfield, MD, Rady Chilidren's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2014
• Primary Completion (Actual): February 1, 2018
• Study Completion (Actual): February 13, 2018

Study Registration Dates

• First Submitted: January 13, 2014
• First Submitted That Met QC Criteria: January 14, 2014
• First Posted (Estimated): January 16, 2014

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 21, 2025
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases, Papulosquamous; Skin Diseases; Psoriasis
• Other Study ID Numbers: LP0076-1017

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO