Chronic Plaque Psoriasis
Conditions
Keywords
Calcitriol, Psoriasis, PK, Adolescents
Brief summary
This is an open-label, multicenter study to assess the systemic exposure to calcitriol in the adolescent population. Calcitriol 3µg/g ointment (2 mg/cm² per application) is to be applied twice daily to involved skin (10 - 35% BSA involved, excluding face, scalp and intertriginous areas) for 56 days (8 weeks). Full Pharmacokinetic (PK) and Pharmacodynamic (PD) profile will be collected during the first 3 weeks of the study; safety and efficacy data will be collected for the 8 weeks of the treatment.
Interventions
DRUGCalcitriol 3mcg/g
Calcitriol 3mcg/g ointment applied twice daily for 56 weeks.
Sponsors
Galderma R&D
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of chronic plaque psoriasis * 10 - 35% BSA of involved skin * Age 12 - 17
Exclusion criteria
* Other type of psoriasis (other than plaque) * Significant abnormal lab findings * Vit D insufficiency
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time at Which Maximum Concentration (Cmax) Occurred (Tmax) | Day 0 (Baseline), Day 21 | Tmax is the time to reach maximum concentration and was reported for calcitriol. |
| Trough Plasma Levels (Ctrough) of Calcitriol | Day 0 (Baseline), Day 14, Day 21, and Day 56 | Trough plasma levels (Ctrough) of calcitriol was reported. |
| The Observed Peak Drug Concentration (Cmax) of Calcitriol | Day 0 (Baseline), Day 21 | Cmax of calcitriol was reported. |
| Area Under the Concentration-Time Curve From Pre-Application (T0) Through 9 Hours Post Dosing (AUC [0-9 Hours]) | 0 (predose) and 9 hours post dose on Day 0 (Baseline), Day 21 | The AUC(0-9 hours) that is area under the plasma concentration-time curve from time 0 to 9 hours after dosing was reported. |
| Area Under the Concentration-Time Curve From Pre-Application (T0) Through 12 Hours Post Dosing (AUC [0-12 Hours]) | 0 (predose) and 12 hours post dose on Day 0 (Baseline), Day 21 | The AUC(0-12 hours) that is area under the plasma concentration-time curve from time 0 to 12 hours after dosing was reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Effect of Calcitriol Ointment on Calcium (Serum Calcium Albumin Adjusted) Homeostasis up to Day 56 | From baseline (Day 0) up to Day 56 | Calcium homeostasis was analyzed with serum calcium albumin adjusted, serum calcium, urinary calcium/creatinine ratio, urinary (U) calcium random as parameters. Change from baseline in the effect of calcitriol ointment on calcium (serum calcium albumin adjusted) homeostasis up to Day 56 was reported. |
| Change From Baseline in Effect of Calcitriol Ointment on Calcium (Urinary Calcium/Creatinine Ratio) Homeostasis up to Day 56 | From baseline (Day 0) up to Day 56 | Calcium homeostasis was analyzed with serum calcium albumin adjusted, serum calcium, urinary calcium/creatinine ratio, urinary (U) calcium random as parameters. Change from baseline in the effect of calcitriol ointment on calcium (urinary calcium/creatinine ratio) homeostasis up to Day 56 was reported. |
| Number of Participants With Adverse Events | From start of the study to Day 56 | An adverse event (AE) was any unfavorable and unintended sign (including an abnormal laboratory finding assessed as clinically significant and different from the baseline visit), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. Number of participants with adverse events were reported. |
| Change From Baseline in Effect of Calcitriol Ointment on Calcium (Serum Calcium, Urinary (U) Calcium Random) and Phosphorus Homeostasis up to Day 56 | From baseline (Day 0) up to Day 56 | Calcium homeostasis was analyzed with serum calcium albumin adjusted, serum calcium, urinary calcium/creatinine ratio, urinary (U) calcium random as parameters. Phosphorus homeostasis was analyzed with phosphorus as parameter. Change from baseline in the effect of calcitriol ointment on calcium (serum calcium, U calcium random) and phosphorus homeostasis up to Day 56 was reported. |
Countries
Canada, United States
Participant flow
Recruitment details
The study was conducted in 7 sites (5 in United States and 2 in Canada) between 01 Aug 2006 (first participant enrolled) to 24 Sep 2009 (last participant completed).
Pre-assignment details
A total of 25 participants were enrolled and completed the study.
Participants by arm
| Arm | Count |
|---|---|
| Calcitriol 3mcg/g Participants received calcitriol 3 micrograms per gram (mcg/g) ointment applied topically twice daily for 56 days. | 25 |
| Total | 25 |
Baseline characteristics
| Characteristic | Calcitriol 3mcg/g |
|---|---|
| Age, Categorical <=18 years | 25 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Age, Continuous | 14.7 Years STANDARD_DEVIATION 1.63 |
| Race/Ethnicity, Customized Race Asian | 1 Participants |
| Race/Ethnicity, Customized Race Black | 2 Participants |
| Race/Ethnicity, Customized Race Caucasian | 16 Participants |
| Race/Ethnicity, Customized Race Hispanic | 4 Participants |
| Race/Ethnicity, Customized Race Other | 2 Participants |
| Sex: Female, Male Female | 14 Participants |
| Sex: Female, Male Male | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 25 |
| other Total, other adverse events | 8 / 25 |
| serious Total, serious adverse events | 0 / 25 |
Outcome results
Primary
Area Under the Concentration-Time Curve From Pre-Application (T0) Through 12 Hours Post Dosing (AUC [0-12 Hours])
The AUC(0-12 hours) that is area under the plasma concentration-time curve from time 0 to 12 hours after dosing was reported.
Time frame: 0 (predose) and 12 hours post dose on Day 0 (Baseline), Day 21
Population: Safety population consisted all participants in the ITT population who had applied the study medication at least once.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Calcitriol 3mcg/g | Area Under the Concentration-Time Curve From Pre-Application (T0) Through 12 Hours Post Dosing (AUC [0-12 Hours]) | Day 21 | 737.74 pg.h/mL | Standard Deviation 203.74 |
| Calcitriol 3mcg/g | Area Under the Concentration-Time Curve From Pre-Application (T0) Through 12 Hours Post Dosing (AUC [0-12 Hours]) | Day 0 (Baseline) | 764.74 pg.h/mL | Standard Deviation 230.003 |
Primary
Area Under the Concentration-Time Curve From Pre-Application (T0) Through 9 Hours Post Dosing (AUC [0-9 Hours])
The AUC(0-9 hours) that is area under the plasma concentration-time curve from time 0 to 9 hours after dosing was reported.
Time frame: 0 (predose) and 9 hours post dose on Day 0 (Baseline), Day 21
Population: Safety population consisted of all participants in the ITT population who had applied the study medication at least once.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Calcitriol 3mcg/g | Area Under the Concentration-Time Curve From Pre-Application (T0) Through 9 Hours Post Dosing (AUC [0-9 Hours]) | Day 0 (Baseline) | 575.12 Picograms. hours per millilitre(pg.h/mL) | Standard Deviation 181.761 |
| Calcitriol 3mcg/g | Area Under the Concentration-Time Curve From Pre-Application (T0) Through 9 Hours Post Dosing (AUC [0-9 Hours]) | Day 21 | 549.29 Picograms. hours per millilitre(pg.h/mL) | Standard Deviation 155.277 |
Primary
The Observed Peak Drug Concentration (Cmax) of Calcitriol
Cmax of calcitriol was reported.
Time frame: Day 0 (Baseline), Day 21
Population: Safety population consisted of all participants in the ITT population who had applied the study medication at least once.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Calcitriol 3mcg/g | The Observed Peak Drug Concentration (Cmax) of Calcitriol | Day 0 (Baseline) | 75.74 pg/mL | Standard Deviation 24.337 |
| Calcitriol 3mcg/g | The Observed Peak Drug Concentration (Cmax) of Calcitriol | Day 21 | 73.18 pg/mL | Standard Deviation 21.514 |
Primary
Time at Which Maximum Concentration (Cmax) Occurred (Tmax)
Tmax is the time to reach maximum concentration and was reported for calcitriol.
Time frame: Day 0 (Baseline), Day 21
Population: Safety population consisted of all participants in the ITT population who had applied the study medication at least once.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Calcitriol 3mcg/g | Time at Which Maximum Concentration (Cmax) Occurred (Tmax) | Day 0 (Baseline) | 4.00 hours |
| Calcitriol 3mcg/g | Time at Which Maximum Concentration (Cmax) Occurred (Tmax) | Day 21 | 3.97 hours |
Primary
Trough Plasma Levels (Ctrough) of Calcitriol
Trough plasma levels (Ctrough) of calcitriol was reported.
Time frame: Day 0 (Baseline), Day 14, Day 21, and Day 56
Population: Safety population consisted of all participants in the ITT population who had applied the study medication at least once.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Calcitriol 3mcg/g | Trough Plasma Levels (Ctrough) of Calcitriol | Day 0 (Baseline) | 65.04 Picograms Per Millilitre (pg/mL) | Standard Deviation 18.851 |
| Calcitriol 3mcg/g | Trough Plasma Levels (Ctrough) of Calcitriol | Day 14 | 62.53 Picograms Per Millilitre (pg/mL) | Standard Deviation 17.742 |
| Calcitriol 3mcg/g | Trough Plasma Levels (Ctrough) of Calcitriol | Day 21 | 61.87 Picograms Per Millilitre (pg/mL) | Standard Deviation 17.703 |
| Calcitriol 3mcg/g | Trough Plasma Levels (Ctrough) of Calcitriol | Day 56 | 61.46 Picograms Per Millilitre (pg/mL) | Standard Deviation 22.811 |
Secondary
Change From Baseline in Effect of Calcitriol Ointment on Calcium (Serum Calcium Albumin Adjusted) Homeostasis up to Day 56
Calcium homeostasis was analyzed with serum calcium albumin adjusted, serum calcium, urinary calcium/creatinine ratio, urinary (U) calcium random as parameters. Change from baseline in the effect of calcitriol ointment on calcium (serum calcium albumin adjusted) homeostasis up to Day 56 was reported.
Time frame: From baseline (Day 0) up to Day 56
Population: Safety population consisted all participants in the ITT population who had applied the study medication at least once.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Calcitriol 3mcg/g | Change From Baseline in Effect of Calcitriol Ointment on Calcium (Serum Calcium Albumin Adjusted) Homeostasis up to Day 56 | -0.01 Millimoles Per Litre (mmol/L) | Standard Deviation 0.083 |
Secondary
Change From Baseline in Effect of Calcitriol Ointment on Calcium (Serum Calcium, Urinary (U) Calcium Random) and Phosphorus Homeostasis up to Day 56
Calcium homeostasis was analyzed with serum calcium albumin adjusted, serum calcium, urinary calcium/creatinine ratio, urinary (U) calcium random as parameters. Phosphorus homeostasis was analyzed with phosphorus as parameter. Change from baseline in the effect of calcitriol ointment on calcium (serum calcium, U calcium random) and phosphorus homeostasis up to Day 56 was reported.
Time frame: From baseline (Day 0) up to Day 56
Population: Safety population consisted of all participants in the ITT population who had applied the study medication at least once.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Calcitriol 3mcg/g | Change From Baseline in Effect of Calcitriol Ointment on Calcium (Serum Calcium, Urinary (U) Calcium Random) and Phosphorus Homeostasis up to Day 56 | Serum Calcium | 0.08 milligrams per deciliter (Mg/dL) | Standard Deviation 0.254 |
| Calcitriol 3mcg/g | Change From Baseline in Effect of Calcitriol Ointment on Calcium (Serum Calcium, Urinary (U) Calcium Random) and Phosphorus Homeostasis up to Day 56 | Urinary (U) Calcium Random | 1.00 milligrams per deciliter (Mg/dL) | Standard Deviation 6.767 |
| Calcitriol 3mcg/g | Change From Baseline in Effect of Calcitriol Ointment on Calcium (Serum Calcium, Urinary (U) Calcium Random) and Phosphorus Homeostasis up to Day 56 | Phosphorus | 0.20 milligrams per deciliter (Mg/dL) | Standard Deviation 0.641 |
Secondary
Change From Baseline in Effect of Calcitriol Ointment on Calcium (Urinary Calcium/Creatinine Ratio) Homeostasis up to Day 56
Calcium homeostasis was analyzed with serum calcium albumin adjusted, serum calcium, urinary calcium/creatinine ratio, urinary (U) calcium random as parameters. Change from baseline in the effect of calcitriol ointment on calcium (urinary calcium/creatinine ratio) homeostasis up to Day 56 was reported.
Time frame: From baseline (Day 0) up to Day 56
Population: Safety population consisted of all participants in the ITT population who had applied the study medication at least once.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Calcitriol 3mcg/g | Change From Baseline in Effect of Calcitriol Ointment on Calcium (Urinary Calcium/Creatinine Ratio) Homeostasis up to Day 56 | 0.01 Ratio | Standard Deviation 0.076 |
Secondary
Number of Participants With Adverse Events
An adverse event (AE) was any unfavorable and unintended sign (including an abnormal laboratory finding assessed as clinically significant and different from the baseline visit), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. Number of participants with adverse events were reported.
Time frame: From start of the study to Day 56
Population: Safety population consisted of all participants in the ITT population who had applied the study medication at least once.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Calcitriol 3mcg/g | Number of Participants With Adverse Events | 13 Participants |