Trial Outcomes & Findings for Effect of LEO 90100 on the HPA Axis and Calcium Metabolism in Subjects With Extensive Psoriasis VulgarisExtensive Psoriasis Vulgaris (NCT NCT01600222)

NCT ID: NCT01600222

Last Updated: 2025-03-07

Results Overview

HPA-axis testing by means of the rapid standard-dose cosyntropin test (ACTH-challenge test) for detection of adrenal suppression.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 37 participants
• Primary outcome timeframe: Day 28
• Results posted on: 2025-03-07

Participant Flow

First Subject First Visit: 4-Jun-2012 Last Subject Last Visit: 2-May-2013

Subjects with extensive psoriasis vulgaris of at least moderate severity (according to the Investigators Global Assessment of Disease Severity; IGA) on the trunk, limbs and the scalp were enrolled. Screening: normal HPA axis function before and after ACTH-challenge test and albumin-corrected serum Ca lvl below the upper normal limit were required.

Participant milestones

Measure	LEO 90100 LEO 90100: Calcipotriol 50 mcg/g (as hydrate) and betamethasone 0.5 mg/g (as dipropionate) Once daily for up to 4 weeks
Overall Study STARTED	37
Overall Study COMPLETED	35
Overall Study NOT COMPLETED	2

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	LEO 90100 n=37 Participants LEO 90100: Calcipotriol 50 mcg/g (as hydrate) and betamethasone 0.5 mg/g (as dipropionate)
Age, Continuous	48.0 years STANDARD_DEVIATION 14.1 • n=5 Participants
Sex: Female, Male Female	17 Participants n=5 Participants
Sex: Female, Male Male	20 Participants n=5 Participants

PRIMARY outcome

Timeframe: Day 28

Population: Per protocol analysis set.

HPA-axis testing by means of the rapid standard-dose cosyntropin test (ACTH-challenge test) for detection of adrenal suppression.

Outcome measures

Measure	LEO 90100 n=35 Participants LEO 90100: Calcipotriol 50 mcg/g (as hydrate) and betamethasone 0.5 mg/g (as dipropionate)
Subjects With Serum Cortisol Concentration of ≤18 mcg/dl at 30 Minutes After Adrenocorticotrophic Hormone-challenge (ACTH-challenge)	0 Subjects

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	LEO 90100 n=37 Participants LEO 90100: Calcipotriol 50 mcg/g (as hydrate) and betamethasone 0.5 mg/g (as dipropionate)
Change in Albumin-corrected Serum Calcium From Baseline to Day 28	0.014 mmol/L Standard Deviation 0.202

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	LEO 90100 n=37 Participants LEO 90100: Calcipotriol 50 mcg/g (as hydrate) and betamethasone 0.5 mg/g (as dipropionate)
Change in 24-hour Urinary Calcium Excretion From Baseline to Day 28	-0.49 mmol/24H Standard Deviation 1.37

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	LEO 90100 n=37 Participants LEO 90100: Calcipotriol 50 mcg/g (as hydrate) and betamethasone 0.5 mg/g (as dipropionate)
Change in 24-hour Urinary Calcium:Creatinine Ratio From Baseline to Day 28	-0.0300 mmol/g Standard Deviation 1.3997

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	LEO 90100 n=35 Participants LEO 90100: Calcipotriol 50 mcg/g (as hydrate) and betamethasone 0.5 mg/g (as dipropionate)
Number of Subjects With Serum Cortisol Concentration of ≤18 mcg/dl at 30 and 60 Minutes After ACTH-challenge at Day 28	0 Subjects

SECONDARY outcome

Timeframe: 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".

Outcome measures

Measure	LEO 90100 n=37 Participants LEO 90100: Calcipotriol 50 mcg/g (as hydrate) and betamethasone 0.5 mg/g (as dipropionate)
Number of Participants With an Adverse Drug Reaction (ADR)	1 participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	LEO 90100 n=37 Participants LEO 90100: Calcipotriol 50 mcg/g (as hydrate) and betamethasone 0.5 mg/g (as dipropionate)
Change in Serum Phosphate From Baseline to Day 28	0.030 mmol/L Standard Deviation 0.145

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	LEO 90100 n=37 Participants LEO 90100: Calcipotriol 50 mcg/g (as hydrate) and betamethasone 0.5 mg/g (as dipropionate)
Change in 24-hour Urinary Phosphate Excretion From Baseline to Day 28	-0.25 mmol/24H Standard Deviation 8.67

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	LEO 90100 n=37 Participants LEO 90100: Calcipotriol 50 mcg/g (as hydrate) and betamethasone 0.5 mg/g (as dipropionate)
Change in Urinary Phosphate: Creatinine Ratio From Baseline to Day 28	1.847 mmol/g Standard Deviation 6.215

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	LEO 90100 n=37 Participants LEO 90100: Calcipotriol 50 mcg/g (as hydrate) and betamethasone 0.5 mg/g (as dipropionate)
Change in Serum Alkaline Phosphatase (ALP) From Baseline to Day 28	-1.5 IU/L Standard Deviation 12.5

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	LEO 90100 n=37 Participants LEO 90100: Calcipotriol 50 mcg/g (as hydrate) and betamethasone 0.5 mg/g (as dipropionate)
Change in Plasma Parathyroid Hormone (PTH) From Baseline to Day 28	0.893 pmol/L Standard Deviation 2.207

SECONDARY outcome

Timeframe: Baseline and Day 28

The effect of LEO 90100 on calcium metabolism was evaluated based on vital sign assessments (blood pressure).

Outcome measures

Measure	LEO 90100 n=37 Participants LEO 90100: Calcipotriol 50 mcg/g (as hydrate) and betamethasone 0.5 mg/g (as dipropionate)
Change in Blood Pressure From Baseline to Day 28 Diastolic Blood Pressure (mmHg)	-1.5 mmHg Standard Deviation 6.2
Change in Blood Pressure From Baseline to Day 28 Systolic Blood Pressure (mmHg)	-2.2 mmHg Standard Deviation 8.1

SECONDARY outcome

Timeframe: Baseline and Day 28

The effect of LEO 90100 on calcium metabolism was evaluated based on vital sign assessments (heart rate).

Outcome measures

Measure	LEO 90100 n=37 Participants LEO 90100: Calcipotriol 50 mcg/g (as hydrate) and betamethasone 0.5 mg/g (as dipropionate)
Change in Heart Rate From Baseline to Day 28	0.2 beats/min Standard Deviation 10.4

SECONDARY outcome

Timeframe: Baseline to Day 28

Number of subjects who discontinued from the study due to adverse events.

Outcome measures

Measure	LEO 90100 n=37 Participants LEO 90100: Calcipotriol 50 mcg/g (as hydrate) and betamethasone 0.5 mg/g (as dipropionate)
Number of Subjects Who Discontinued From the Study	0 participants

SECONDARY outcome

Timeframe: 4 weeks / 28 days

Population: Plasma samples for PK assessment were collected from all 37 subjects however; PK samples from 2 subjects were only collected at screening (SV2) and at Day 14. Therefore these 2 subjects were excluded from PK analysis. Summary of PK parameters based on those subjects that had quantifiable plasma concentrations.

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.

Outcome measures

Measure	LEO 90100 n=35 Participants LEO 90100: Calcipotriol 50 mcg/g (as hydrate) and betamethasone 0.5 mg/g (as dipropionate)
Pharmacokinetic Evaluation Cmax Betamethasone dipropionate (BDP) (n=5)	52.2 pg/ml Interval 33.7 to 81.1
Pharmacokinetic Evaluation Cmax betamethasone 17- propionate (n=27)	148 pg/ml Interval 30.2 to 1133.0
Pharmacokinetic Evaluation Cmax calcipotriol (n=1)	55.9 pg/ml Interval 55.9 to 55.9
Pharmacokinetic Evaluation Cmax MC1080 (n=5)	24.4 pg/ml Interval 23.3 to 26.6

SECONDARY outcome

Timeframe: 4 weeks / 28 days

Population: Plasma samples for PK assessment were collected from all 37 subjects however; PK samples from 2 subjects were only collected at screening (SV2) and at Day 14. Therefore these 2 subjects were excluded from PK analysis. Summary of PK parameters based on those subjects that had quantifiable plasma concentrations

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.

Outcome measures

Measure	LEO 90100 n=35 Participants LEO 90100: Calcipotriol 50 mcg/g (as hydrate) and betamethasone 0.5 mg/g (as dipropionate)
Pharmacokinetic Evaluation AUClast betamethasone 17- propionate (n=27)	683.6 pg/ml Interval 18.5 to 4254.0
Pharmacokinetic Evaluation AUClast Betamethasone dipropionate (BDP) (n=5)	36.5 pg/ml Interval 16.9 to 82.5
Pharmacokinetic Evaluation AUClast calcipotriol (n=1)	82.5 pg/ml Interval 82.5 to 82.5
Pharmacokinetic Evaluation AUClast MC1080 (n=5)	59.3 pg/ml Interval 55.3 to 65.5

SECONDARY outcome

Timeframe: 4 weeks / 28 days

Population: Plasma samples for PK assessment were collected from all 37 subjects however; PK samples from 2 subjects were only collected at screening (SV2) and at Day 14. Therefore these 2 subjects were excluded from PK analysis. Summary of PK parameters based on those subjects that had quantifiable plasma concentrations

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.

Outcome measures

Measure	LEO 90100 n=35 Participants LEO 90100: Calcipotriol 50 mcg/g (as hydrate) and betamethasone 0.5 mg/g (as dipropionate)
Pharmacokinetic Evaluation AUCinf Betamethasone dipropionate (BDP) (n=5)	NA pg/ml It was not possible to estimate λz (elimination phase rate constant) to calculate AUCinf for any of the 4 analytes after use of LEO 90100 (assay sensitivity limitations, insufficient plasma concentration data in the terminal phase of PK curves).
Pharmacokinetic Evaluation AUCinf betamethasone 17- propionate (n=27)	NA pg/ml It was not possible to estimate λz (elimination phase rate constant) to calculate AUCinf for any of the 4 analytes after use of LEO 90100 (assay sensitivity limitations, insufficient plasma concentration data in the terminal phase of PK curves).
Pharmacokinetic Evaluation AUCinf calcipotriol (n=1)	NA pg/ml It was not possible to estimate λz (elimination phase rate constant) to calculate AUCinf for any of the 4 analytes after use of LEO 90100 (assay sensitivity limitations, insufficient plasma concentration data in the terminal phase of PK curves).
Pharmacokinetic Evaluation AUCinf MC1080 (n=5)	NA pg/ml It was not possible to estimate λz (elimination phase rate constant) to calculate AUCinf for any of the 4 analytes after use of LEO 90100 (assay sensitivity limitations, insufficient plasma concentration data in the terminal phase of PK curves).

SECONDARY outcome

Timeframe: 4 weeks / 28 days

Population: Plasma samples for PK assessment were collected from all 37 subjects however; PK samples from 2 subjects were only collected at screening (SV2) and at Day 14. Therefore these 2 subjects were excluded from PK analysis. Summary of PK parameters based on those subjects that had quantifiable plasma concentrations

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.

Outcome measures

Measure	LEO 90100 n=35 Participants LEO 90100: Calcipotriol 50 mcg/g (as hydrate) and betamethasone 0.5 mg/g (as dipropionate)
Pharmacokinetic Evaluation Tmax MC1080 (n=5)	5.0000 h Interval 3.0 to 5.0
Pharmacokinetic Evaluation Tmax Betamethasone dipropionate (BDP) (n=5)	1.0000 h Interval 1.0 to 3.05
Pharmacokinetic Evaluation Tmax betamethasone 17- propionate (n=27)	2.0830 h Interval 0.0 to 7.05
Pharmacokinetic Evaluation Tmax calcipotriol (n=1)	2.000 h Interval 2.0 to 2.0

SECONDARY outcome

Timeframe: 4 weeks / 28 days

Population: Plasma samples for PK assessment were collected from all 37 subjects however; PK samples from 2 subjects were only collected at screening (SV2) and at Day 14. Therefore these 2 subjects were excluded from PK analysis. Summary of PK parameters based on those subjects that had quantifiable plasma concentrations

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.

Outcome measures

Measure	LEO 90100 n=35 Participants LEO 90100: Calcipotriol 50 mcg/g (as hydrate) and betamethasone 0.5 mg/g (as dipropionate)
Pharmacokinetic Evaluation T1/2 Betamethasone dipropionate (BDP) (n=5)	NA h It was not possible to estimate λz (elimination phase rate constant) to calculate T1/2 for any of the 4 analytes after use of LEO 90100 (assay sensitivity limitations, insufficient plasma concentration data in the terminal phase of PK curves).
Pharmacokinetic Evaluation T1/2 betamethasone 17- propionate (n=27)	NA h It was not possible to estimate λz (elimination phase rate constant) to calculate T1/2 for any of the 4 analytes after use of LEO 90100 (assay sensitivity limitations, insufficient plasma concentration data in the terminal phase of PK curves).
Pharmacokinetic Evaluation T1/2 calcipotriol (n=1)	NA h It was not possible to estimate λz (elimination phase rate constant) to calculate T1/2 for any of the 4 analytes after use of LEO 90100 (assay sensitivity limitations, insufficient plasma concentration data in the terminal phase of PK curves).
Pharmacokinetic Evaluation T1/2 MC1080 (n=5)	NA h It was not possible to estimate λz (elimination phase rate constant) to calculate T1/2 for any of the 4 analytes after use of LEO 90100 (assay sensitivity limitations, insufficient plasma concentration data in the terminal phase of PK curves).

SECONDARY outcome

Timeframe: 4 weeks I 28 days and End of treatment

Population: The percentage of subjects achieving controlled disease on Day 28 (n=35) was calculated from the full analysis set. The percentage of subjects achieving controlled disease at End of Treatment (n=37) was was calculated from the full analysis set using a last observation carried forward approach.

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.

Outcome measures

Measure	LEO 90100 n=37 Participants LEO 90100: Calcipotriol 50 mcg/g (as hydrate) and betamethasone 0.5 mg/g (as dipropionate)
Efficacy Evaluation Day 28 (n=35)	48.6 percentage of subjects
Efficacy Evaluation End of treatment (n=37)	45.9 percentage of subjects

Adverse Events

LEO 90100

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	LEO 90100 n=37 participants at risk LEO 90100: Calcipotriol 50 mcg/g (as hydrate) and betamethasone 0.5 mg/g (as dipropionate)
Infections and infestations Fungal infection	2.7% 1/37 • Number of events 1
Musculoskeletal and connective tissue disorders Arthralgia	2.7% 1/37 • Number of events 1
Nervous system disorders Headache	2.7% 1/37 • Number of events 1
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	2.7% 1/37 • Number of events 1
Respiratory, thoracic and mediastinal disorders Upper-airway cough syndrome	2.7% 1/37 • Number of events 1
Skin and subcutaneous tissue disorders Erythema	2.7% 1/37 • Number of events 1

Additional Information

Clinical Trial Disclosure Manager

LEO Pharma A/S

Phone: +45 44945888

Email: ctr.disclosure@leo-pharma.com

Results disclosure agreements

• Principal investigator is a sponsor employee LEO acknowledges the investigators right to publish the entire results of the study, irrespective of outcome. LEO retains the right to have any publication submitted to LEO for review. Investigators must undertake not to submit any part of their individual data for publication without the prior consent of LEO.
• Publication restrictions are in place

Restriction type: OTHER