Trial Outcomes & Findings for Efficacy and Safety Study of CD 2027 Spray in Subjects With Plaque-type Psoriasis (NCT NCT00763555)

Results Overview

Success Rate 1 was defined as percentage of participants who achieved at least 2-grade improvement from Baseline on Global Severity Score (GSS) at Week 8. GSS is a 5-point scale which ranges from 0-4, where 0 = clear, 1 = almost clear, 2 = mild, 3 = moderate, 4 = severe, higher score indicated higher severity. All missing values were imputed by last observation carried forward (LOCF).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

88 participants

Primary outcome timeframe

Week 8

Results posted on

2022-08-23

Participant Flow

The study was conducted at 6 centers in United States and Canada between 22 September 2008 and 23 January 2009.

A total of 111 participants were screened in the study. Out of which, 88 participants were randomized to receive Calcitriol 3 micrograms per gram (mcg/g) spray or its vehicle.

Participant milestones

Participant milestones
Measure	Calcitriol 3 mcg/g Spray Participants applied Calcitriol 3 mcg/g spray topically to the affected areas twice daily for 8 weeks.	Calcitriol Vehicle Participants applied placebo matched to Calcitriol 3 mcg/g spray topically to the affected areas twice daily for 8 weeks.
Overall Study STARTED	44	44
Overall Study COMPLETED	40	34
Overall Study NOT COMPLETED	4	10

Reasons for withdrawal

Reasons for withdrawal
Measure	Calcitriol 3 mcg/g Spray Participants applied Calcitriol 3 mcg/g spray topically to the affected areas twice daily for 8 weeks.	Calcitriol Vehicle Participants applied placebo matched to Calcitriol 3 mcg/g spray topically to the affected areas twice daily for 8 weeks.
Overall Study Adverse Event	2	1
Overall Study Withdrawal by Subject	2	6
Overall Study Lost to Follow-up	0	3

Baseline Characteristics

Efficacy and Safety Study of CD 2027 Spray in Subjects With Plaque-type Psoriasis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Calcitriol 3 mcg/g Spray n=44 Participants Participants applied Calcitriol 3 mcg/g spray topically to the affected areas twice daily for 8 weeks.	Calcitriol Vehicle n=44 Participants Participants applied placebo matched to Calcitriol 3 mcg/g spray topically to the affected areas twice daily for 8 weeks.	Total n=88 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	41 Participants n=5 Participants	36 Participants n=7 Participants	77 Participants n=5 Participants
Age, Categorical >=65 years	3 Participants n=5 Participants	8 Participants n=7 Participants	11 Participants n=5 Participants
Sex: Female, Male Female	20 Participants n=5 Participants	12 Participants n=7 Participants	32 Participants n=5 Participants
Sex: Female, Male Male	24 Participants n=5 Participants	32 Participants n=7 Participants	56 Participants n=5 Participants
Race/Ethnicity, Customized Caucasian	42 Participants n=5 Participants	40 Participants n=7 Participants	82 Participants n=5 Participants
Race/Ethnicity, Customized Black	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Race/Ethnicity, Customized Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Other	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants

PRIMARY outcome

Timeframe: Week 8

Population: ITT population is defined as all participants who were randomized and to whom medication is dispensed.

Success Rate 1 was defined as percentage of participants who achieved at least 2-grade improvement from Baseline on Global Severity Score (GSS) at Week 8. GSS is a 5-point scale which ranges from 0-4, where 0 = clear, 1 = almost clear, 2 = mild, 3 = moderate, 4 = severe, higher score indicated higher severity. All missing values were imputed by last observation carried forward (LOCF).

Outcome measures

Outcome measures
Measure	Calcitriol 3 mcg/g Spray n=44 Participants Participants applied Calcitriol 3 mcg/g spray topically to the affected areas twice daily for 8 weeks.	Calcitriol Vehicle n=44 Participants Participants applied placebo matched to Calcitriol 3 mcg/g spray topically to the affected areas twice daily for 8 weeks.
Percentage of Participants With Success Rate 1 (SR1) at Week 8	4.5 percentage of participants	0.0 percentage of participants

PRIMARY outcome

Timeframe: Week 8

Population: ITT population is defined as all participants who were randomized and to whom medication is dispensed.

Success Rate 2 was defined as percentage of participants who achieved "clear" or "almost clear" on GSS at Week 8. GSS is a 5-point scale which ranges from 0-4, where 0 = clear, 1 = almost clear, 2 = mild, 3 = moderate, 4 = severe, higher score indicated higher severity. All missing values were imputed by last observation carried forward (LOCF).

Outcome measures

Outcome measures
Measure	Calcitriol 3 mcg/g Spray n=44 Participants Participants applied Calcitriol 3 mcg/g spray topically to the affected areas twice daily for 8 weeks.	Calcitriol Vehicle n=44 Participants Participants applied placebo matched to Calcitriol 3 mcg/g spray topically to the affected areas twice daily for 8 weeks.
Percentage of Participants With Success Rate 2 (SR2) at Week 8	4.5 percentage of participants	0.0 percentage of participants

PRIMARY outcome

Timeframe: Baseline, Week 8

Population: ITT population is defined as all participants who were randomized and to whom medication is dispensed.

DSS is the sum of all the individual score of evaluated target lesion that includes plaque elevation (abnormal thickness of the psoriasis lesion), erythema (abnormal redness of the skin), and scaling (shedding of the stratum corneum). Each individual parameters evaluated the affected area by using a 5-point scale ranging from 0 to 4, that is, 0 = None; 1 = Mild; 2 = Moderate; 3 = Severe and 4 =Very severe, where higher score indicated worst condition. All missing values were imputed by last observation carried forward (LOCF). The total score of each parameter ranges from 0-12, where higher score indicated worst condition.

Outcome measures

Outcome measures
Measure	Calcitriol 3 mcg/g Spray n=44 Participants Participants applied Calcitriol 3 mcg/g spray topically to the affected areas twice daily for 8 weeks.	Calcitriol Vehicle n=44 Participants Participants applied placebo matched to Calcitriol 3 mcg/g spray topically to the affected areas twice daily for 8 weeks.
Change From Baseline in Dermatologic Sum Score (DSS) at Week 8	-1.2 score on a scale Standard Deviation 1.66	-1.0 score on a scale Standard Deviation 1.55

PRIMARY outcome

Timeframe: Baseline, Week 8

Population: ITT population is defined as all participants who were randomized and to whom medication is dispensed.

Erythema (abnormal redness of skin) score is a 5-point scale: 0=None (No detectable erythema. Skin of normal color); 1=Mild (Slight pinkness present); 2=Moderate (Definite redness, easily recognized); 3=Severe (Intense redness) and 4=Severe (Very Intense redness). Scaling (shedding of stratum corneum) score is a 5- point scale: 0=None (No shedding); 1=Mild (Barely perceptible shedding, noticeable only on light scratching or rubbing); 2=Moderate (Obvious but not profuse shedding); 3=Severe (heavy scale production) and 4=Very severe (very thick scales). Plaque elevation (abnormal thickness of psoriasis lesion) score was a 5- point scale: 0=None (Normal skin thickness. No elevation of skin); 1=Mild (Barely perceptible elevation (by touching) of psoriasis plaques); 2=Moderate (Obvious elevation above normal skin level; moderate thickening); 3=Severe (definite thick elevation above normal skin level) and 4=Severe (Very thick elevation).

Outcome measures

Outcome measures
Measure	Calcitriol 3 mcg/g Spray n=44 Participants Participants applied Calcitriol 3 mcg/g spray topically to the affected areas twice daily for 8 weeks.	Calcitriol Vehicle n=44 Participants Participants applied placebo matched to Calcitriol 3 mcg/g spray topically to the affected areas twice daily for 8 weeks.
Percentage of Participants With at Least 1-Grade Improvement From Baseline in Erythema, Scaling and Plaque Elevation Erythema	38.6 percentage of participants	25.0 percentage of participants
Percentage of Participants With at Least 1-Grade Improvement From Baseline in Erythema, Scaling and Plaque Elevation Scaling	40.9 percentage of participants	36.4 percentage of participants
Percentage of Participants With at Least 1-Grade Improvement From Baseline in Erythema, Scaling and Plaque Elevation Plaque elevation	34.1 percentage of participants	36.4 percentage of participants

SECONDARY outcome

Timeframe: up to Week 8

Population: The Safety population is defined as all participants in the ITT population who have applied the study medication at least once.

AE was any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily had a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory value), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.

Outcome measures

Outcome measures
Measure	Calcitriol 3 mcg/g Spray n=44 Participants Participants applied Calcitriol 3 mcg/g spray topically to the affected areas twice daily for 8 weeks.	Calcitriol Vehicle n=44 Participants Participants applied placebo matched to Calcitriol 3 mcg/g spray topically to the affected areas twice daily for 8 weeks.
Number of Participants With Adverse Events (AEs)	11 Participants	9 Participants

SECONDARY outcome

Timeframe: up to Week 8

Population: The Safety population is defined as all participants in the ITT population who have applied the study medication at least once.

Local tolerability skin assessments were performed by the investigator and based on 5-point scale which ranges from 0 to 4. 0 = none (no evidence of local intolerance); 1=mild (minimal erythema and/or edema, slight glazed appearance); 2 = moderate (definite erythema and/or edema with peeling and/or cracking but needs no adaptation of posology); 3 = severe (erythema, edema glazing with fissures, few vesicles or papules) and 4 = very severe (strong reaction spreading beyond the treated area, bullous reaction, erosions). Higher grades indicated worsening of condition. Percentage of participants with increase in score by Week 8 from baseline has been presented here, where the row titles indicate participant's new scores by Week 8.

Outcome measures

Outcome measures
Measure	Calcitriol 3 mcg/g Spray n=44 Participants Participants applied Calcitriol 3 mcg/g spray topically to the affected areas twice daily for 8 weeks.	Calcitriol Vehicle n=44 Participants Participants applied placebo matched to Calcitriol 3 mcg/g spray topically to the affected areas twice daily for 8 weeks.
Percentage of Participants With a Local Tolerability Score Worse Than Baseline Score 1 = mild	4.5 percentage of participants	7.0 percentage of participants
Percentage of Participants With a Local Tolerability Score Worse Than Baseline Score 2 = moderate	2.3 percentage of participants	0.0 percentage of participants
Percentage of Participants With a Local Tolerability Score Worse Than Baseline Score 3 = severe	2.3 percentage of participants	4.7 percentage of participants
Percentage of Participants With a Local Tolerability Score Worse Than Baseline Score 4 = very severe	2.3 percentage of participants	2.3 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Week 8

Population: The Safety population is defined as all participants in the ITT population who have applied the study medication at least once. Here, "Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.

Change from baseline in calcitriol plasma levels were reported.

Outcome measures

Outcome measures
Measure	Calcitriol 3 mcg/g Spray n=43 Participants Participants applied Calcitriol 3 mcg/g spray topically to the affected areas twice daily for 8 weeks.	Calcitriol Vehicle n=40 Participants Participants applied placebo matched to Calcitriol 3 mcg/g spray topically to the affected areas twice daily for 8 weeks.
Change From Baseline in Calcitriol Plasma Levels	-2.89 picograms per milliliter (pg/mL) Standard Deviation 23.971	-8.82 picograms per milliliter (pg/mL) Standard Deviation 22.873

SECONDARY outcome

Timeframe: Baseline, Week 8

Population: The Safety population is defined as all participants in the ITT population who have applied the study medication at least once. Here, "Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.

Change from baseline in serum calcium homeostasis parameter (Albumin) were reported.

Outcome measures

Outcome measures
Measure	Calcitriol 3 mcg/g Spray n=43 Participants Participants applied Calcitriol 3 mcg/g spray topically to the affected areas twice daily for 8 weeks.	Calcitriol Vehicle n=40 Participants Participants applied placebo matched to Calcitriol 3 mcg/g spray topically to the affected areas twice daily for 8 weeks.
Change From Baseline in Serum Calcium Homeostasis Parameter: Albumin	-0.16 grams per deciliter (g/dL) Standard Deviation 0.253	-0.08 grams per deciliter (g/dL) Standard Deviation 0.230

SECONDARY outcome

Timeframe: Baseline, Week 8

Population: The Safety population is defined as all participants in the ITT population who have applied the study medication at least once. Here, "Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.

Change from baseline in serum calcium homeostasis parameter (Albumin-adjusted calcium) were reported.

Outcome measures

Outcome measures
Measure	Calcitriol 3 mcg/g Spray n=43 Participants Participants applied Calcitriol 3 mcg/g spray topically to the affected areas twice daily for 8 weeks.	Calcitriol Vehicle n=40 Participants Participants applied placebo matched to Calcitriol 3 mcg/g spray topically to the affected areas twice daily for 8 weeks.
Change From Baseline in Serum Calcium Homeostasis Parameter: Albumin-adjusted Calcium	0.07 milligrams per deciliter (mg/dL) Standard Deviation 0.310	0.03 milligrams per deciliter (mg/dL) Standard Deviation 0.262

SECONDARY outcome

Timeframe: Baseline, Week 8

Population: The Safety population is defined as all participants in the ITT population who have applied the study medication at least once. Here, "Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.

Change from baseline in serum calcium homeostasis parameter (Calcium) were reported.

Outcome measures

Outcome measures
Measure	Calcitriol 3 mcg/g Spray n=43 Participants Participants applied Calcitriol 3 mcg/g spray topically to the affected areas twice daily for 8 weeks.	Calcitriol Vehicle n=40 Participants Participants applied placebo matched to Calcitriol 3 mcg/g spray topically to the affected areas twice daily for 8 weeks.
Change From Baseline in Serum Calcium Homeostasis Parameter: Calcium	-0.09 mg/dL Standard Deviation 0.283	-0.05 mg/dL Standard Deviation 0.328

SECONDARY outcome

Timeframe: Baseline, Week 8

Population: The Safety population is defined as all participants in the ITT population who have applied the study medication at least once. Here, "Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.

Change from baseline in serum calcium homeostasis parameter (Phosphorus) were reported.

Outcome measures

Outcome measures
Measure	Calcitriol 3 mcg/g Spray n=43 Participants Participants applied Calcitriol 3 mcg/g spray topically to the affected areas twice daily for 8 weeks.	Calcitriol Vehicle n=40 Participants Participants applied placebo matched to Calcitriol 3 mcg/g spray topically to the affected areas twice daily for 8 weeks.
Change From Baseline in Serum Calcium Homeostasis Parameter: Phosphorus	-0.07 mg/dL Standard Deviation 0.437	0.02 mg/dL Standard Deviation 0.535

SECONDARY outcome

Timeframe: Baseline, Week 8

Population: The Safety population is defined as all participants in the ITT population who have applied the study medication at least once. Here, "Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure

Change from baseline in serum calcium homeostasis parameter (PTH intact) were reported.

Outcome measures

Outcome measures
Measure	Calcitriol 3 mcg/g Spray n=43 Participants Participants applied Calcitriol 3 mcg/g spray topically to the affected areas twice daily for 8 weeks.	Calcitriol Vehicle n=40 Participants Participants applied placebo matched to Calcitriol 3 mcg/g spray topically to the affected areas twice daily for 8 weeks.
Change From Baseline in Serum Calcium Homeostasis Parameter: Parathyroid Hormone (PTH) Intact	7.16 pg/mL Standard Deviation 25.215	5.15 pg/mL Standard Deviation 18.480

SECONDARY outcome

Timeframe: Baseline, Week 8

Population: The Safety population is defined as all participants in the ITT population who have applied the study medication at least once. Here, "Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.

Change from baseline in Blood Chemistry: Alkaline Phosphatase, AST and ALT were reported.

Outcome measures

Outcome measures
Measure	Calcitriol 3 mcg/g Spray n=43 Participants Participants applied Calcitriol 3 mcg/g spray topically to the affected areas twice daily for 8 weeks.	Calcitriol Vehicle n=40 Participants Participants applied placebo matched to Calcitriol 3 mcg/g spray topically to the affected areas twice daily for 8 weeks.
Change From Baseline in Blood Chemistry: Alkaline Phosphatase, Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) Alkaline Phosphatase	0.58 international units per liter (IU/L) Standard Deviation 8.362	-1.03 international units per liter (IU/L) Standard Deviation 17.150
Change From Baseline in Blood Chemistry: Alkaline Phosphatase, Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) AST	1.42 international units per liter (IU/L) Standard Deviation 9.014	-0.35 international units per liter (IU/L) Standard Deviation 8.110
Change From Baseline in Blood Chemistry: Alkaline Phosphatase, Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) ALT	0.72 international units per liter (IU/L) Standard Deviation 8.564	-1.75 international units per liter (IU/L) Standard Deviation 11.151

SECONDARY outcome

Timeframe: Baseline, Week 8

Population: The Safety population is defined as all participants in the ITT population who have applied the study medication at least once. Here, "Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.

Change from baseline in Blood Chemistry: Bilirubin Direct, Bilirubin Total, BUN and Creatinine were reported.

Outcome measures

Outcome measures
Measure	Calcitriol 3 mcg/g Spray n=43 Participants Participants applied Calcitriol 3 mcg/g spray topically to the affected areas twice daily for 8 weeks.	Calcitriol Vehicle n=40 Participants Participants applied placebo matched to Calcitriol 3 mcg/g spray topically to the affected areas twice daily for 8 weeks.
Change From Baseline in Blood Chemistry: Bilirubin Direct, Bilirubin Total, Blood Urea Nitrogen (BUN) and Creatinine Bilirubin Direct	-0.02 mg/dL Standard Deviation 0.048	-0.03 mg/dL Standard Deviation 0.054
Change From Baseline in Blood Chemistry: Bilirubin Direct, Bilirubin Total, Blood Urea Nitrogen (BUN) and Creatinine Bilirubin Total	0.01 mg/dL Standard Deviation 0.208	0.03 mg/dL Standard Deviation 0.200
Change From Baseline in Blood Chemistry: Bilirubin Direct, Bilirubin Total, Blood Urea Nitrogen (BUN) and Creatinine BUN	0.65 mg/dL Standard Deviation 3.592	0.55 mg/dL Standard Deviation 3.250
Change From Baseline in Blood Chemistry: Bilirubin Direct, Bilirubin Total, Blood Urea Nitrogen (BUN) and Creatinine Creatinine	-0.01 mg/dL Standard Deviation 0.130	0.03 mg/dL Standard Deviation 0.103

SECONDARY outcome

Timeframe: Baseline, Week 8

Population: The Safety population is defined as all participants in the ITT population who have applied the study medication at least once. Here, "Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.

Change from baseline in vital sign parameter: heart rate was reported.

Outcome measures

Outcome measures
Measure	Calcitriol 3 mcg/g Spray n=40 Participants Participants applied Calcitriol 3 mcg/g spray topically to the affected areas twice daily for 8 weeks.	Calcitriol Vehicle n=34 Participants Participants applied placebo matched to Calcitriol 3 mcg/g spray topically to the affected areas twice daily for 8 weeks.
Change From Baseline in Vital Sign Parameter: Heart Rate	3.1 beats per minute Standard Deviation 7.63	1.4 beats per minute Standard Deviation 8.53

SECONDARY outcome

Timeframe: Baseline, Week 8

Population: The Safety population is defined as all participants in the ITT population who have applied the study medication at least once. Here, "Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.

Change from baseline in vital sign parameter: Systolic Blood Pressure and Diastolic Blood Pressure was reported.

Outcome measures

Outcome measures
Measure	Calcitriol 3 mcg/g Spray n=40 Participants Participants applied Calcitriol 3 mcg/g spray topically to the affected areas twice daily for 8 weeks.	Calcitriol Vehicle n=34 Participants Participants applied placebo matched to Calcitriol 3 mcg/g spray topically to the affected areas twice daily for 8 weeks.
Change From Baseline in Vital Sign Parameter: Systolic Blood Pressure and Diastolic Blood Pressure Systolic Blood Pressure	0.7 millimeter of mercury (mmHg) Standard Deviation 14.03	-1.4 millimeter of mercury (mmHg) Standard Deviation 11.01
Change From Baseline in Vital Sign Parameter: Systolic Blood Pressure and Diastolic Blood Pressure Diastolic Blood Pressure	0.2 millimeter of mercury (mmHg) Standard Deviation 7.43	-1.0 millimeter of mercury (mmHg) Standard Deviation 8.54

Adverse Events

Calcitriol 3 mcg/g Spray

Serious events: 1 serious events

Other events: 10 other events

Deaths: 0 deaths

Calcitriol Vehicle

Serious events: 1 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Calcitriol 3 mcg/g Spray n=44 participants at risk Participants applied Calcitriol 3 mcg/g spray topically to the affected areas twice daily for 8 weeks.	Calcitriol Vehicle n=44 participants at risk Participants applied placebo matched to Calcitriol 3 mcg/g spray topically to the affected areas twice daily for 8 weeks.
Cardiac disorders Coronary artery disease	2.3% 1/44 • up to Week 8 The Safety population is defined as all participants in the ITT population who have applied the study medication at least once.	0.00% 0/44 • up to Week 8 The Safety population is defined as all participants in the ITT population who have applied the study medication at least once.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/44 • up to Week 8 The Safety population is defined as all participants in the ITT population who have applied the study medication at least once.	2.3% 1/44 • up to Week 8 The Safety population is defined as all participants in the ITT population who have applied the study medication at least once.

Other adverse events

Additional Information

Clinical Operations

Galderma

Phone: 817 961 5000

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: OTHER

Measure	Calcitriol 3 mcg/g Spray n=44 participants at risk Participants applied Calcitriol 3 mcg/g spray topically to the affected areas twice daily for 8 weeks.	Calcitriol Vehicle n=44 participants at risk Participants applied placebo matched to Calcitriol 3 mcg/g spray topically to the affected areas twice daily for 8 weeks.
Infections and infestations Nasopharyngitis	6.8% 3/44 • up to Week 8 The Safety population is defined as all participants in the ITT population who have applied the study medication at least once.	4.5% 2/44 • up to Week 8 The Safety population is defined as all participants in the ITT population who have applied the study medication at least once.
Infections and infestations Pharyngitis	4.5% 2/44 • up to Week 8 The Safety population is defined as all participants in the ITT population who have applied the study medication at least once.	0.00% 0/44 • up to Week 8 The Safety population is defined as all participants in the ITT population who have applied the study medication at least once.
Infections and infestations Gastroenteritis	2.3% 1/44 • up to Week 8 The Safety population is defined as all participants in the ITT population who have applied the study medication at least once.	0.00% 0/44 • up to Week 8 The Safety population is defined as all participants in the ITT population who have applied the study medication at least once.
Infections and infestations Sinusitis	2.3% 1/44 • up to Week 8 The Safety population is defined as all participants in the ITT population who have applied the study medication at least once.	0.00% 0/44 • up to Week 8 The Safety population is defined as all participants in the ITT population who have applied the study medication at least once.
Infections and infestations Upper respiratory tract infection	2.3% 1/44 • up to Week 8 The Safety population is defined as all participants in the ITT population who have applied the study medication at least once.	2.3% 1/44 • up to Week 8 The Safety population is defined as all participants in the ITT population who have applied the study medication at least once.
Infections and infestations Pneumonia	0.00% 0/44 • up to Week 8 The Safety population is defined as all participants in the ITT population who have applied the study medication at least once.	2.3% 1/44 • up to Week 8 The Safety population is defined as all participants in the ITT population who have applied the study medication at least once.
Infections and infestations Urinary tract infection	0.00% 0/44 • up to Week 8 The Safety population is defined as all participants in the ITT population who have applied the study medication at least once.	2.3% 1/44 • up to Week 8 The Safety population is defined as all participants in the ITT population who have applied the study medication at least once.
Investigations Blood calcium increased	2.3% 1/44 • up to Week 8 The Safety population is defined as all participants in the ITT population who have applied the study medication at least once.	0.00% 0/44 • up to Week 8 The Safety population is defined as all participants in the ITT population who have applied the study medication at least once.
Investigations Blood cholesterol increased	2.3% 1/44 • up to Week 8 The Safety population is defined as all participants in the ITT population who have applied the study medication at least once.	0.00% 0/44 • up to Week 8 The Safety population is defined as all participants in the ITT population who have applied the study medication at least once.
Investigations Blood pressure increased	2.3% 1/44 • up to Week 8 The Safety population is defined as all participants in the ITT population who have applied the study medication at least once.	0.00% 0/44 • up to Week 8 The Safety population is defined as all participants in the ITT population who have applied the study medication at least once.
Investigations Aspartate aminotransferase increased	0.00% 0/44 • up to Week 8 The Safety population is defined as all participants in the ITT population who have applied the study medication at least once.	2.3% 1/44 • up to Week 8 The Safety population is defined as all participants in the ITT population who have applied the study medication at least once.
Nervous system disorders Headache	2.3% 1/44 • up to Week 8 The Safety population is defined as all participants in the ITT population who have applied the study medication at least once.	0.00% 0/44 • up to Week 8 The Safety population is defined as all participants in the ITT population who have applied the study medication at least once.
Reproductive system and breast disorders Menorrhagia	2.3% 1/44 • up to Week 8 The Safety population is defined as all participants in the ITT population who have applied the study medication at least once.	0.00% 0/44 • up to Week 8 The Safety population is defined as all participants in the ITT population who have applied the study medication at least once.
Skin and subcutaneous tissue disorders Psoriasis	2.3% 1/44 • up to Week 8 The Safety population is defined as all participants in the ITT population who have applied the study medication at least once.	0.00% 0/44 • up to Week 8 The Safety population is defined as all participants in the ITT population who have applied the study medication at least once.
Skin and subcutaneous tissue disorders Skin burning sensation	0.00% 0/44 • up to Week 8 The Safety population is defined as all participants in the ITT population who have applied the study medication at least once.	2.3% 1/44 • up to Week 8 The Safety population is defined as all participants in the ITT population who have applied the study medication at least once.
Skin and subcutaneous tissue disorders Skin irritation	0.00% 0/44 • up to Week 8 The Safety population is defined as all participants in the ITT population who have applied the study medication at least once.	2.3% 1/44 • up to Week 8 The Safety population is defined as all participants in the ITT population who have applied the study medication at least once.
Gastrointestinal disorders Diarrhoea	0.00% 0/44 • up to Week 8 The Safety population is defined as all participants in the ITT population who have applied the study medication at least once.	2.3% 1/44 • up to Week 8 The Safety population is defined as all participants in the ITT population who have applied the study medication at least once.
Respiratory, thoracic and mediastinal disorders Rales	0.00% 0/44 • up to Week 8 The Safety population is defined as all participants in the ITT population who have applied the study medication at least once.	2.3% 1/44 • up to Week 8 The Safety population is defined as all participants in the ITT population who have applied the study medication at least once.