Trial Outcomes & Findings for Efficacy of Alitretinoin Treatment in Patients With Pustular Form of Psoriasis (NCT NCT01245140)

The study was conducted at 7 centers from 26 April 2011 to 16 April 2014, in male and female participants of Palmo-plantar pustulosis (PPP), aged \>= 18 years.

The total study duration was 33 weeks, with a Screening Period of up to 4 weeks, followed by 24 weeks of treatment and a 5-week safety Follow-up Period. Participants who met eligibility criteria were randomized (2:1) to receive 30 milligrams (mg) alitretinoin or matching placebo, given orally as gelatin capsules, once daily (QD) for up to 24 weeks.

Efficacy of Alitretinoin Treatment in Patients With Pustular Form of Psoriasis

The investigator evaluated the PPPASI score on a 5-point scale. The parameters of erythema, total number of pustules, and desquamation were scored for the right/left palm and the right/left sole. After correcting the scores for area (based on a 7-point scale) and the site involved (palm or sole), the PPPASI score per palm/sole was produced. The final PPPASI score was calculated as the sum of the PPPASI score for the right sole + the PPPASI score for the left sole + the PPPASI score for the right palm + the PPPASI score for the left palm and ranges from 0 (no palmo-plantar pustulosis psoriasis \[PPP\]) to 72 (most severe PPP). Change from Baseline is defined as value at the EOT minus the Baseline value.

The investigator evaluated the PPPASI score on a 5-point scale. The parameters of erythema, total number of pustules, and desquamation were scored for the right/left palm and the right/left sole. After correcting the scores for area (based on a 7-point scale) and the site involved (palm or sole), the PPPASI score per palm/sole was produced. The final PPPASI score was calculated as the sum of the PPPASI score for the right sole + the PPPASI score for the left sole + the PPPASI score for the right palm + the PPPASI score for the left palm and ranges from 0 (no palmo-plantar pustulosis psoriasis \[PPP\]) to 72 (most severe PPP). Change from Baseline is defined as value at the EOT minus the Baseline value. PPPASI 50 response and PPPASI 75 response are defined as a 50% and 75% decrease, respectively, in the PPPASI score from Baseline.

The overall number of fresh and older pustules on the left and right palms and soles was assessed at Baseline, at each visit during the treatment period (Weeks 4, 8, 12, 16, and 20), and at the EOT visit. The total pustule count was calculated as the sum of the pustule count for the left/right palm and left/right sole.

The overall number of fresh and older pustules on the left and right palms and soles was assessed at Baseline, at each visit during the treatment period (Weeks 4, 8, 12, 16, and 20), and at the End of Treatment visit. The total pustule count was calculated as the sum of the pustule count for the left/right palm and left/right sole. Change from Baseline is defined as the value at the post-Baseline visit minus the Baseline value.

Psoriatic plaques were graded based on three criteria: redness (R), thickness (T), and scaliness (S). Severity was rated for each criterion on a 5-point scale (0=no involvement, up to 4=severe involvement). Fraction of the total surface area affected on the head, upper extremities, trunk, and lower extremities was graded on a 7-point scale (0=no involvement, up to 6=greater than 90% involvement). The four body regions were weighted to reflect their respective proportion of body surface area, and the composite mPASI score for all body regions was calculated based on the redness, thickness, and scaliness scores of plaques (0-4 each) for the head, upper extremities, trunk, and lower extremities and the area of psoriatic involvement score (0-6). The lowest possible mPASI score was zero and highest up to 72; Higher score values represents greater severity of psoriasis. mPASI scores were continuous, with 0.1 increments within these values.

Psoriatic plaques were graded based on three criteria: redness (R), thickness (T), and scaliness (S). Severity was rated for each criterion on a 5-point scale (0=no involvement, up to 4=severe involvement). Fraction of the total surface area affected on the head, upper extremities, trunk, and lower extremities was graded on a 7-point scale (0=no involvement, up to 6=greater than 90% involvement). The four body regions were weighted to reflect their respective proportion of body surface area, and the composite mPASI score for all body regions was calculated based on redness, thickness, and scaliness scores of plaques (0-4 each) for head, upper extremities, trunk, lower extremities and area of psoriatic involvement score (0-6). Lowest possible mPASI score was 0 and highest up to 72; Higher score values represents greater severity of psoriasis. mPASI scores were continuous, with 0.1 increments within these values. Change from Baseline is defined as the value at EOT minus baseline value.

Psoriatic plaques were graded based on three criteria: redness (R), thickness (T), and scaliness (S). Severity was rated for each criterion on a 5-point scale (0=no involvement, up to 4=severe involvement). The fraction of the total surface area affected on the head, upper extremities, trunk, and lower extremities was graded on a 7-point scale (0=no involvement, up to 6=greater than 90% involvement). The four body regions were weighted to reflect their respective proportion of body surface area, and the composite mPASI score for all body regions was calculated. mPASI 50 response and mPASI 75 response is defined as a 50% and 75% decrease, respectively, in the mPASI score from Baseline.

The severity of nail lesions was assessed for all participants with psoriatic nail involvement by obtaining the NAPSI score. Scores were taken for fingernails only. No scores were taken for participants with traumatic or fungal changes in nails. The nail was divided into four quadrants, each of which was rated with a 0 or 1, based on the absence (0) or presence (1) of pathological signs resulting from involvement of both the nail matrix and the nail bed. Each nail was given a score for nail bed psoriasis (0-4) and nail matrix psoriasis (0-4) depending on the presence of nail psoriasis in that quadrant. Possible scores for matrix and nail bed psoriasis: 0=none, 1=present in 1/4 nail, 2=present in 2/4 nail, 3=present in 3/4 nail, 4=present in 4/4 nail. NAPSI score for nail matrix (0-4) and nail bed (0-4) were reported at Baseline, Week 12, and at the EOT visit (Week 24).

The severity of nail lesions was assessed for all participants with psoriatic nail involvement by obtaining the NAPSI score. Scores were taken for fingernails only. No scores were taken for participants with traumatic or fungal changes in nails. The nail was divided into four quadrants, each of which was rated with a 0 or 1, based on the absence (0) or presence (1) of pathological signs resulting from involvement of both the nail matrix and the nail bed. Each nail was given a score for nail bed psoriasis (0-4) and nail matrix psoriasis (0-4) depending on the presence of nail psoriasis in that quadrant. Possible scores for matrix and nail bed psoriasis: 0=none, 1=present in 1/4 nail, 2=present in 2/4 nail, 3=present in 3/4 nail, 4=present in 4/4 nail. NAPSI score for nail matrix (0-4) and nail bed (0-4) were reported at Baseline, Week 12, and at the EOT visit (Week 24). Change from Baseline is defined as the value at the post-Baseline visit minus the Baseline value.

An AE was any adverse change from the participant's Baseline (pre-treatment) clinical condition, including intercurrent illness, which occurred during the course of a clinical study after written informed consent had been given, whether considered related to treatment or not. The relationship of AEs to the study treatment was assessed as unrelated, remotely related, possibly related, and probably related. For an AE to be considered serious, it fell into one or more of the following categories: results in death, is life threatening, results in persistent or significant disability/incapacity, results in or prolongs inpatient hospitalization, and is a congenital abnormality or birth defect.

Fasted lipid laboratory parameters included triglycerides, total cholesterol, high-density lipoprotein (HDL) cholesterol, and low-density lipoprotein (LDL) cholesterol. Change from Baseline is defined as the value at the post-Baseline visit minus the Baseline value.

Change from Baseline is defined as the value at the safety follow up visit minus baseline value.

Laboratory parameters included triglycerides, total cholesterol, HDL cholesterol, LDL cholesterol, LDL/HDL ratio, alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, and amylase and lipase. The central laboratory classified a finding as either abnormal or normal.

The CES-D scale is a short, self-report scale designed to measure depressive symptomatology in the general population. The CES-D consists of 20 questions. Participants were instructed to circle the number for each statement that best described how often they felt or behaved a particular way during the past week. The score was the sum of the weights of the 20 items. Responses range from 0 to 3 for each item (0=rarely or none of the time, 1=some or little of the time, 2=moderately or much of the time, 3=most or almost all the time). The CES-D score ranges from 0 to 60, with higher scores indicating greater depression. Participants with a CES-D score of 20 or higher were re-evaluated within 2 weeks. If a CES-D score of 20 or higher was confirmed on the second occasion, and if the score represents an increase over Baseline of 4 points or more, study treatment was interrupted and the participants were referred for psychiatric evaluation.

The CES-D scale is a short, self-report scale designed to measure depressive symptomatology in the general population. The CES-D consists of 20 questions. Participants were instructed to circle the number for each statement that best described how often they felt or behaved a particular way during the past week. The score was the sum of the weights of the 20 items. Responses range from 0 to 3 for each item (0=rarely or none of the time, 1=some or little of the time, 2=moderately or much of the time, 3=most or almost all the time). The CES-D score ranges from 0 to 60, with higher scores indicating greater depression. Participants with a CES-D score of \>=20 were re-evaluated within 2 weeks. If a CES-D score of \>=20 was confirmed on the second occasion, and if the score represents an increase over BL of 4 points or more, study treatment was interrupted and the participants were referred for psychiatric evaluation. Change from BL is defined as the post-BL value minus the BL value.

The assessment of suicidality was conducted using the CSSRS, a brief questionnaire designed to assess severity and change in suicidality using a semi-structured interview to probe participant responses. The suicidal ideation intensity total score was the sum of suicidal ideation severity rating scores for frequency, duration, controllability, deterrents, and reasons for ideation. For each item, each participant got an intensity score from 0(none) to 5(worst). Therefore, the suicidal ideation intensity total score range from 0 to 25, with a score of 0 given for no suicidal ideation. CSSRS scores were reported at Screening; Baseline; Week 4, 8, 12, 16, 20; EOT (Week 24);and safety follow-up (Week 29).

The assessment of suicidality was conducted using the CSSRS, a brief questionnaire designed to assess severity and change in suicidality using a semi-structured interview to probe participant responses. The suicidal ideation intensity total score was the sum of suicidal ideation severity rating scores for frequency, duration, controllability, deterrents, and reasons for ideation. For each item, each participant got an intensity score from 0(none) to 5(worst). Therefore, the suicidal ideation intensity total score range from 0 to 25, with a score of 0 given for no suicidal ideation. CSSRS scores were reported at Baseline; Week 4, 8, 12, 16, 20; EOT (Week 24); and safety follow-up (Week 29). Change from Baseline is defined as the value at the post-Baseline visit minus the Baseline value.

SBP and DBP were assessed at Screening, Baseline, and EOT.

HR is defined as the rate at which the heart beats.

Body weight was measured at Screening, Baseline, and EOT.

Change from Baseline is defined as the value at EOT minus the Baseline value.

HR is defined as the rate at which the heart beats. Change from Baseline is defined as the value at EOT minus the Baseline value.

Change from Baseline is defined as the value at EOT minus the value at Baseline.

A physical examination for each participant was performed at Baseline and at EOT (Week 24). The primary investigator classified physical status as either normal or abnormal.

Serum pregnancy tests were performed at each visit for females of childbearing potential.