Trial Outcomes & Findings for A Study to Evaluate the Safety and Effectiveness of Doxercalciferol Capsules in Participants With Moderate to Severe Psoriasis (NCT NCT00601107)

Last Updated: 2014-05-05

Results Overview

PASI score: range: 0 (no disease) to 72 (maximal disease). Body was divided into head (h), trunk (t), upper (u) and lower (l) extremities. For each section, percent area of skin involved (A) was estimated: 1 (\<10%) to 6 (90% - 100%), and severity was estimated by clinical signs: (erythema \[E\], induration \[I\], and desquamation \[D\]) on a scale: 0=no symptoms, 4=very marked. PASI score= 0.1 (E\[h\] + I\[h\] + D\[h\]) A\[h\] + 0.2 (E\[u\] + I\[u\] + D\[u\]) A\[u\] + 0.3 (E\[t\] + I\[t\] + D\[t\]) A\[t\] + 0.4 (E\[l\] + l\[I\] + D\[l\]) A\[l\].

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

111 participants

Primary outcome timeframe

Week 12 or Early Termination

Results posted on

2014-05-05

Participant Flow

The study was conducted at 19 centers in the United States of America between April 01, 2008 and June 09, 2009.

A total of 195 participants were screened of which 84 (43.1%) were screen failures; main reason for screen failure was participant did not qualify for randomization. A total of 111 participants were randomized.

Participant milestones

Participant milestones
Measure	Placebo Placebo matching to doxercalciferol capsules orally once daily up to Week 24.	Doxercalciferol 2.5 mcg/Day Doxercalciferol 2.5 microgram (mcg) capsule orally once daily up to Week 24.	Doxercalciferol 5 mcg/Day Doxercalciferol 5 mcg capsules orally once daily up to Week 24.	Doxercalciferol 7.5 mcg/Day Doxercalciferol 7.5 mcg capsules orally once daily up to Week 24.
Overall Study STARTED	27	31	28	25
Overall Study Treated	27	31	28	25
Overall Study COMPLETED	14	22	16	13
Overall Study NOT COMPLETED	13	9	12	12

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Placebo matching to doxercalciferol capsules orally once daily up to Week 24.	Doxercalciferol 2.5 mcg/Day Doxercalciferol 2.5 microgram (mcg) capsule orally once daily up to Week 24.	Doxercalciferol 5 mcg/Day Doxercalciferol 5 mcg capsules orally once daily up to Week 24.	Doxercalciferol 7.5 mcg/Day Doxercalciferol 7.5 mcg capsules orally once daily up to Week 24.
Overall Study Adverse Event	0	1	3	0
Overall Study Withdrawal by Subject	5	4	7	4
Overall Study Lost to Follow-up	3	3	0	3
Overall Study Serum Calcium >11.5 milligram/deciliter	0	0	0	1
Overall Study Worsening of Psoriasis	4	1	1	4
Overall Study Undefined	1	0	1	0

Baseline Characteristics

A Study to Evaluate the Safety and Effectiveness of Doxercalciferol Capsules in Participants With Moderate to Severe Psoriasis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=27 Participants Placebo matching to doxercalciferol capsules orally once daily up to Week 24.	Doxercalciferol 2.5 mcg/Day n=31 Participants Doxercalciferol 2.5 microgram (mcg) capsule orally once daily up to Week 24.	Doxercalciferol 5 mcg/Day n=28 Participants Doxercalciferol 5 mcg capsules orally once daily up to Week 24.	Doxercalciferol 7.5 mcg/Day n=25 Participants Doxercalciferol 7.5 mcg capsules orally once daily up to Week 24.	Total n=111 Participants Total of all reporting groups
Age, Continuous	44.0 years STANDARD_DEVIATION 11.9 • n=5 Participants	40.5 years STANDARD_DEVIATION 12.4 • n=7 Participants	49.9 years STANDARD_DEVIATION 12.6 • n=5 Participants	44.2 years STANDARD_DEVIATION 16.3 • n=4 Participants	44.5 years STANDARD_DEVIATION 13.6 • n=21 Participants
Sex: Female, Male Female	9 Participants n=5 Participants	11 Participants n=7 Participants	10 Participants n=5 Participants	10 Participants n=4 Participants	40 Participants n=21 Participants
Sex: Female, Male Male	18 Participants n=5 Participants	20 Participants n=7 Participants	18 Participants n=5 Participants	15 Participants n=4 Participants	71 Participants n=21 Participants
Race/Ethnicity, Customized Asian	1 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants	0 participants n=4 Participants	3 participants n=21 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	2 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants	2 participants n=21 Participants
Race/Ethnicity, Customized Black or African American	2 participants n=5 Participants	3 participants n=7 Participants	0 participants n=5 Participants	2 participants n=4 Participants	7 participants n=21 Participants
Race/Ethnicity, Customized White	22 participants n=5 Participants	27 participants n=7 Participants	26 participants n=5 Participants	22 participants n=4 Participants	97 participants n=21 Participants
Race/Ethnicity, Customized Multiple	0 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants	1 participants n=4 Participants	2 participants n=21 Participants
Body Mass Index (BMI)	32.4 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 7.5 • n=5 Participants	33.9 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 8.3 • n=7 Participants	30.1 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 6.5 • n=5 Participants	32.7 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 9.8 • n=4 Participants	32.3 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 8.1 • n=21 Participants
Week 0/Day 1 Psoriasis Area Severity Index (PASI) Score Less Than or Equal to (<=) 16	15 participants n=5 Participants	16 participants n=7 Participants	16 participants n=5 Participants	14 participants n=4 Participants	61 participants n=21 Participants
Week 0/Day 1 Psoriasis Area Severity Index (PASI) Score Greater Than (>) 16	12 participants n=5 Participants	15 participants n=7 Participants	12 participants n=5 Participants	11 participants n=4 Participants	50 participants n=21 Participants

PRIMARY outcome

Timeframe: Week 12 or Early Termination

Population: The Full Analysis Set (FAS) included all safety set-evaluable participants with at least one post-baseline PASI assessment after the date of first dose in the treatment period.

Outcome measures

Outcome measures
Measure	Placebo n=25 Participants Placebo matching to doxercalciferol capsules orally once daily up to Week 24.	Doxercalciferol 2.5 mcg/Day n=30 Participants Doxercalciferol 2.5 microgram (mcg) capsule orally once daily up to Week 24.	Doxercalciferol 5 mcg/Day n=28 Participants Doxercalciferol 5 mcg capsules orally once daily up to Week 24.	Doxercalciferol 7.5 mcg/Day n=25 Participants Doxercalciferol 7.5 mcg capsules orally once daily up to Week 24.
Percentage of Participants With at Least 50 Percent (%) Reduction in Psoriasis Area Severity Index (PASI) Score at Week 12 or Early Termination	20.0 percentage of participants	20.0 percentage of participants	17.9 percentage of participants	20.0 percentage of participants

SECONDARY outcome

Timeframe: Week 24 or Early Termination

Population: FAS included all safety set-evaluable participants with at least one post-baseline PASI assessment after the date of first dose in the treatment period.

Outcome measures

Outcome measures
Measure	Placebo n=25 Participants Placebo matching to doxercalciferol capsules orally once daily up to Week 24.	Doxercalciferol 2.5 mcg/Day n=30 Participants Doxercalciferol 2.5 microgram (mcg) capsule orally once daily up to Week 24.	Doxercalciferol 5 mcg/Day n=28 Participants Doxercalciferol 5 mcg capsules orally once daily up to Week 24.	Doxercalciferol 7.5 mcg/Day n=25 Participants Doxercalciferol 7.5 mcg capsules orally once daily up to Week 24.
Percentage of Participants With at Least 50 Percent (%) Reduction in Psoriasis Area Severity Index (PASI) Score at Week 24 or Early Termination	36.0 percentage of participants	20.0 percentage of participants	21.4 percentage of participants	32.0 percentage of participants

SECONDARY outcome

Timeframe: Week 12 or Early Termination, Week 24 or Early Termination

Population: FAS included all safety set-evaluable participants with at least one post-baseline PASI assessment after the date of first dose in the treatment period.

Static PGA of psoriasis is scored on a 5-point scale (0 = clear to 4 = severe), reflecting a global consideration of the erythema, induration and scaling across all psoriatic lesions. Clear (erythema: no, scale: no, induration: no thickness); Almost Clear (erythema: light pink, scale: fine scale, induration: barely palpable); Mild (erythema: light red, scale: coarse scale on most lesions, induration: slight but visible elevation, indistinct edges); Moderate (erythema: red, scale: coarse adherent scale predominates, induration: moderate elevation with edges); and Severe (erythema: dark red to purple, scale: thickened adherent scale, induration: marked thickness distinct and pronounced edges). Percentage of participants with static PGA score of clear or almost clear are reported.

Outcome measures

Outcome measures
Measure	Placebo n=25 Participants Placebo matching to doxercalciferol capsules orally once daily up to Week 24.	Doxercalciferol 2.5 mcg/Day n=30 Participants Doxercalciferol 2.5 microgram (mcg) capsule orally once daily up to Week 24.	Doxercalciferol 5 mcg/Day n=28 Participants Doxercalciferol 5 mcg capsules orally once daily up to Week 24.	Doxercalciferol 7.5 mcg/Day n=25 Participants Doxercalciferol 7.5 mcg capsules orally once daily up to Week 24.
Percentage of Participants With Static Physician's Global Assessment (PGA) Score of Clear or Almost Clear at Week 12, 24 or Early Termination Week 24 or Early Termination	8.0 percentage of participants	3.3 percentage of participants	10.7 percentage of participants	16.0 percentage of participants
Percentage of Participants With Static Physician's Global Assessment (PGA) Score of Clear or Almost Clear at Week 12, 24 or Early Termination Week 12 or Early Termination	0 percentage of participants	6.7 percentage of participants	3.6 percentage of participants	0 percentage of participants

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Doxercalciferol 2.5 mcg/Day

Serious events: 2 serious events

Other events: 16 other events

Deaths: 0 deaths

Doxercalciferol 5 mcg/Day

Serious events: 1 serious events

Other events: 14 other events

Deaths: 0 deaths

Doxercalciferol 7.5 mcg/Day

Serious events: 1 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=27 participants at risk Placebo matching to doxercalciferol capsules orally once daily up to Week 24.	Doxercalciferol 2.5 mcg/Day n=31 participants at risk Doxercalciferol 2.5 microgram (mcg) capsule orally once daily up to Week 24.	Doxercalciferol 5 mcg/Day n=28 participants at risk Doxercalciferol 5 mcg capsules orally once daily up to Week 24.	Doxercalciferol 7.5 mcg/Day n=25 participants at risk Doxercalciferol 7.5 mcg capsules orally once daily up to Week 24.
Cardiac disorders Atrial fibrillation	0.00% 0/27 • Reported adverse events include the treatment-emergent events starting on or after the day of study drug administration up to Week 28 or Early Termination Analysis was performed on Safety Set, defined as all randomized participants who received at least 1 dose of study medication. In the event a single participant experienced both serious and non-serious forms of the same adverse events, the individual was included in the numerator (number of participants affected) of each adverse event table.	0.00% 0/31 • Reported adverse events include the treatment-emergent events starting on or after the day of study drug administration up to Week 28 or Early Termination Analysis was performed on Safety Set, defined as all randomized participants who received at least 1 dose of study medication. In the event a single participant experienced both serious and non-serious forms of the same adverse events, the individual was included in the numerator (number of participants affected) of each adverse event table.	3.6% 1/28 • Reported adverse events include the treatment-emergent events starting on or after the day of study drug administration up to Week 28 or Early Termination Analysis was performed on Safety Set, defined as all randomized participants who received at least 1 dose of study medication. In the event a single participant experienced both serious and non-serious forms of the same adverse events, the individual was included in the numerator (number of participants affected) of each adverse event table.	0.00% 0/25 • Reported adverse events include the treatment-emergent events starting on or after the day of study drug administration up to Week 28 or Early Termination Analysis was performed on Safety Set, defined as all randomized participants who received at least 1 dose of study medication. In the event a single participant experienced both serious and non-serious forms of the same adverse events, the individual was included in the numerator (number of participants affected) of each adverse event table.
Eye disorders Retinal detachment	0.00% 0/27 • Reported adverse events include the treatment-emergent events starting on or after the day of study drug administration up to Week 28 or Early Termination Analysis was performed on Safety Set, defined as all randomized participants who received at least 1 dose of study medication. In the event a single participant experienced both serious and non-serious forms of the same adverse events, the individual was included in the numerator (number of participants affected) of each adverse event table.	3.2% 1/31 • Reported adverse events include the treatment-emergent events starting on or after the day of study drug administration up to Week 28 or Early Termination Analysis was performed on Safety Set, defined as all randomized participants who received at least 1 dose of study medication. In the event a single participant experienced both serious and non-serious forms of the same adverse events, the individual was included in the numerator (number of participants affected) of each adverse event table.	0.00% 0/28 • Reported adverse events include the treatment-emergent events starting on or after the day of study drug administration up to Week 28 or Early Termination Analysis was performed on Safety Set, defined as all randomized participants who received at least 1 dose of study medication. In the event a single participant experienced both serious and non-serious forms of the same adverse events, the individual was included in the numerator (number of participants affected) of each adverse event table.	0.00% 0/25 • Reported adverse events include the treatment-emergent events starting on or after the day of study drug administration up to Week 28 or Early Termination Analysis was performed on Safety Set, defined as all randomized participants who received at least 1 dose of study medication. In the event a single participant experienced both serious and non-serious forms of the same adverse events, the individual was included in the numerator (number of participants affected) of each adverse event table.
Investigations Blood creatinine increased	0.00% 0/27 • Reported adverse events include the treatment-emergent events starting on or after the day of study drug administration up to Week 28 or Early Termination Analysis was performed on Safety Set, defined as all randomized participants who received at least 1 dose of study medication. In the event a single participant experienced both serious and non-serious forms of the same adverse events, the individual was included in the numerator (number of participants affected) of each adverse event table.	0.00% 0/31 • Reported adverse events include the treatment-emergent events starting on or after the day of study drug administration up to Week 28 or Early Termination Analysis was performed on Safety Set, defined as all randomized participants who received at least 1 dose of study medication. In the event a single participant experienced both serious and non-serious forms of the same adverse events, the individual was included in the numerator (number of participants affected) of each adverse event table.	0.00% 0/28 • Reported adverse events include the treatment-emergent events starting on or after the day of study drug administration up to Week 28 or Early Termination Analysis was performed on Safety Set, defined as all randomized participants who received at least 1 dose of study medication. In the event a single participant experienced both serious and non-serious forms of the same adverse events, the individual was included in the numerator (number of participants affected) of each adverse event table.	4.0% 1/25 • Reported adverse events include the treatment-emergent events starting on or after the day of study drug administration up to Week 28 or Early Termination Analysis was performed on Safety Set, defined as all randomized participants who received at least 1 dose of study medication. In the event a single participant experienced both serious and non-serious forms of the same adverse events, the individual was included in the numerator (number of participants affected) of each adverse event table.
Investigations Blood urea increased	0.00% 0/27 • Reported adverse events include the treatment-emergent events starting on or after the day of study drug administration up to Week 28 or Early Termination Analysis was performed on Safety Set, defined as all randomized participants who received at least 1 dose of study medication. In the event a single participant experienced both serious and non-serious forms of the same adverse events, the individual was included in the numerator (number of participants affected) of each adverse event table.	0.00% 0/31 • Reported adverse events include the treatment-emergent events starting on or after the day of study drug administration up to Week 28 or Early Termination Analysis was performed on Safety Set, defined as all randomized participants who received at least 1 dose of study medication. In the event a single participant experienced both serious and non-serious forms of the same adverse events, the individual was included in the numerator (number of participants affected) of each adverse event table.	0.00% 0/28 • Reported adverse events include the treatment-emergent events starting on or after the day of study drug administration up to Week 28 or Early Termination Analysis was performed on Safety Set, defined as all randomized participants who received at least 1 dose of study medication. In the event a single participant experienced both serious and non-serious forms of the same adverse events, the individual was included in the numerator (number of participants affected) of each adverse event table.	4.0% 1/25 • Reported adverse events include the treatment-emergent events starting on or after the day of study drug administration up to Week 28 or Early Termination Analysis was performed on Safety Set, defined as all randomized participants who received at least 1 dose of study medication. In the event a single participant experienced both serious and non-serious forms of the same adverse events, the individual was included in the numerator (number of participants affected) of each adverse event table.
Investigations Glomerular filtration rate decreased	0.00% 0/27 • Reported adverse events include the treatment-emergent events starting on or after the day of study drug administration up to Week 28 or Early Termination Analysis was performed on Safety Set, defined as all randomized participants who received at least 1 dose of study medication. In the event a single participant experienced both serious and non-serious forms of the same adverse events, the individual was included in the numerator (number of participants affected) of each adverse event table.	0.00% 0/31 • Reported adverse events include the treatment-emergent events starting on or after the day of study drug administration up to Week 28 or Early Termination Analysis was performed on Safety Set, defined as all randomized participants who received at least 1 dose of study medication. In the event a single participant experienced both serious and non-serious forms of the same adverse events, the individual was included in the numerator (number of participants affected) of each adverse event table.	0.00% 0/28 • Reported adverse events include the treatment-emergent events starting on or after the day of study drug administration up to Week 28 or Early Termination Analysis was performed on Safety Set, defined as all randomized participants who received at least 1 dose of study medication. In the event a single participant experienced both serious and non-serious forms of the same adverse events, the individual was included in the numerator (number of participants affected) of each adverse event table.	4.0% 1/25 • Reported adverse events include the treatment-emergent events starting on or after the day of study drug administration up to Week 28 or Early Termination Analysis was performed on Safety Set, defined as all randomized participants who received at least 1 dose of study medication. In the event a single participant experienced both serious and non-serious forms of the same adverse events, the individual was included in the numerator (number of participants affected) of each adverse event table.
Metabolism and nutrition disorders Hypercalcaemia	0.00% 0/27 • Reported adverse events include the treatment-emergent events starting on or after the day of study drug administration up to Week 28 or Early Termination Analysis was performed on Safety Set, defined as all randomized participants who received at least 1 dose of study medication. In the event a single participant experienced both serious and non-serious forms of the same adverse events, the individual was included in the numerator (number of participants affected) of each adverse event table.	0.00% 0/31 • Reported adverse events include the treatment-emergent events starting on or after the day of study drug administration up to Week 28 or Early Termination Analysis was performed on Safety Set, defined as all randomized participants who received at least 1 dose of study medication. In the event a single participant experienced both serious and non-serious forms of the same adverse events, the individual was included in the numerator (number of participants affected) of each adverse event table.	0.00% 0/28 • Reported adverse events include the treatment-emergent events starting on or after the day of study drug administration up to Week 28 or Early Termination Analysis was performed on Safety Set, defined as all randomized participants who received at least 1 dose of study medication. In the event a single participant experienced both serious and non-serious forms of the same adverse events, the individual was included in the numerator (number of participants affected) of each adverse event table.	4.0% 1/25 • Reported adverse events include the treatment-emergent events starting on or after the day of study drug administration up to Week 28 or Early Termination Analysis was performed on Safety Set, defined as all randomized participants who received at least 1 dose of study medication. In the event a single participant experienced both serious and non-serious forms of the same adverse events, the individual was included in the numerator (number of participants affected) of each adverse event table.
Reproductive system and breast disorders Endometriosis	0.00% 0/27 • Reported adverse events include the treatment-emergent events starting on or after the day of study drug administration up to Week 28 or Early Termination Analysis was performed on Safety Set, defined as all randomized participants who received at least 1 dose of study medication. In the event a single participant experienced both serious and non-serious forms of the same adverse events, the individual was included in the numerator (number of participants affected) of each adverse event table.	3.2% 1/31 • Reported adverse events include the treatment-emergent events starting on or after the day of study drug administration up to Week 28 or Early Termination Analysis was performed on Safety Set, defined as all randomized participants who received at least 1 dose of study medication. In the event a single participant experienced both serious and non-serious forms of the same adverse events, the individual was included in the numerator (number of participants affected) of each adverse event table.	0.00% 0/28 • Reported adverse events include the treatment-emergent events starting on or after the day of study drug administration up to Week 28 or Early Termination Analysis was performed on Safety Set, defined as all randomized participants who received at least 1 dose of study medication. In the event a single participant experienced both serious and non-serious forms of the same adverse events, the individual was included in the numerator (number of participants affected) of each adverse event table.	0.00% 0/25 • Reported adverse events include the treatment-emergent events starting on or after the day of study drug administration up to Week 28 or Early Termination Analysis was performed on Safety Set, defined as all randomized participants who received at least 1 dose of study medication. In the event a single participant experienced both serious and non-serious forms of the same adverse events, the individual was included in the numerator (number of participants affected) of each adverse event table.
Reproductive system and breast disorders Menorrhagia	0.00% 0/27 • Reported adverse events include the treatment-emergent events starting on or after the day of study drug administration up to Week 28 or Early Termination Analysis was performed on Safety Set, defined as all randomized participants who received at least 1 dose of study medication. In the event a single participant experienced both serious and non-serious forms of the same adverse events, the individual was included in the numerator (number of participants affected) of each adverse event table.	3.2% 1/31 • Reported adverse events include the treatment-emergent events starting on or after the day of study drug administration up to Week 28 or Early Termination Analysis was performed on Safety Set, defined as all randomized participants who received at least 1 dose of study medication. In the event a single participant experienced both serious and non-serious forms of the same adverse events, the individual was included in the numerator (number of participants affected) of each adverse event table.	0.00% 0/28 • Reported adverse events include the treatment-emergent events starting on or after the day of study drug administration up to Week 28 or Early Termination Analysis was performed on Safety Set, defined as all randomized participants who received at least 1 dose of study medication. In the event a single participant experienced both serious and non-serious forms of the same adverse events, the individual was included in the numerator (number of participants affected) of each adverse event table.	0.00% 0/25 • Reported adverse events include the treatment-emergent events starting on or after the day of study drug administration up to Week 28 or Early Termination Analysis was performed on Safety Set, defined as all randomized participants who received at least 1 dose of study medication. In the event a single participant experienced both serious and non-serious forms of the same adverse events, the individual was included in the numerator (number of participants affected) of each adverse event table.

Other adverse events

Additional Information

Trial Transparency Team

Sanofi

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee If no publication has occurred within 12 months of the completion of the study, the Investigator shall have the right to publish/present independently the results of the study. The Investigator shall provide the Sponsor with a copy of any such presentation/publication for comment at least 30 days before any presentation/submission for publication. If requested by the Sponsor, any presentation/submission shall be delayed up to 90 days, to allow the Sponsor to preserve its proprietary rights.
Publication restrictions are in place

Restriction type: OTHER