Phase 2
N=33
Efficacy of Alitretinoin Treatment in Patients With Pustular Form of Psoriasis
Psoriasis
Bottom Line
View on ClinicalTrials.gov: NCT01245140 ↗Enrolled (actual)
33
Serious AEs
3.0%
Results posted
Apr 2017
Primary outcome: Primary: Change From Baseline in the Palmo-plantar Pustulosis Psoriasis Area and Severity Index (PPPASI) Score at the End of Treatment (EOT) (Week 24) or at the Last Assessment — -44.6; -45.2 Scores on a scale — p=0.9705
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- alitretinoin (Drug); Placebo (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Stiefel, a GSK Company
- Primary completion
- Mar 2014
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change From Baseline in the Palmo-plantar Pustulosis Psoriasis Area and Severity Index (PPPASI) Score at the End of Treatment (EOT) (Week 24) or at the Last Assessment |
-44.6; -45.2 | 0.9705 |
| PRIMARY Number of Participants With PPPASI 50 Response and PPPASI 75 Response |
6; 11; 3; 5 | 0.4564 |
| SECONDARY Total Pustule Count at Baseline; Weeks 4, 8, 12, 16, and 20; and at EOT (Week 24) |
82.7; 106.0; 71.6; 31.0; 69.7; 30.4 | — |
| SECONDARY Absolute Change From Baseline (BL) in Total Pustule Count at Weeks 4, 8, 12, 16, and 20 and at EOT (Week 24) |
-11.1; -75.3; -7.9; -75.9; -7.1; -74.2 | 0.51 |
| SECONDARY Mean Modified Psoriasis Area Severity Index (mPASI) Score at Baseline; Weeks 4, 8, 12, 16, and 20; and EOT (Week 24) |
0.2; 0.5; 0.3; 0.4; 0.0; 0.4 | 0.12 |
| SECONDARY Change From Baseline in the mPASI Score at EOT (Week 24) or at the Last Assessment |
-95.8; -51.0 | 0.2358 |
| SECONDARY Number of Participants With mPASI 50 Response and mPASI 75 Response |
3; 2; 3; 2 | 0.1667 |
| SECONDARY Mean Nail Psoriasis Severity Index (NAPSI) Score for Nail Bed Psoriasis and Nail Matrix Psoriasis at Baseline, Week 12, and EOT (Week 24) |
1.1; 1.2; 0.4; 1.3; 1.6; 0.9 | — |
| SECONDARY Absolute Change From Baseline in NAPSI Score for Nail Bed Psoriasis and Nail Matrix Psoriasis at Week 12, and EOT (Week 24) |
-0.4; 0.3; 0.4; -0.3; -1.4; -0.5 | — |
| SECONDARY Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) and an AE/SAE Related to Study Treatment |
8; 18; 6; 15; 0; 1 | — |
| SECONDARY Absolute Change From Baseline in Fasted Lipid Laboratory Test Values at Weeks 4, 8, 12, 16, and 20; EOT (Week 24); and at Safety Follow-up (Week 29) |
0.6; 2.4; 1.0; 3.8; 2.5; 5.8 | — |
| SECONDARY Absolute Change From Baseline in Fasted LDL/HDL Ratio at Weeks 4, 8, 12, 16, and 20; EOT (Week 24); and at Safety Follow-up (Week 29) |
0.0; 0.0; 0.3; 0.7; 0.2; 0.9 | — |
| SECONDARY Number of Participants With the Indicated Shift in the Indicated Laboratory Values From Baseline (BL) to EOT (Week 24) |
0; 2; 0; 0; 1; 1 | — |
| SECONDARY Mean Center for Epidemiological Studies Depression Scale (CES-D) Scores at Screening; Baseline; Weeks 4, 8, 12, 16, and 20; EOT (Week 24); and Safety Follow-up (Week 29) |
7.2; 5.7; 7.0; 4.5; 5.0; 2.9 | — |
| SECONDARY Absolute Change From Baseline (BL) in CES-D Scores at Weeks 4, 8, 12, 16, and 20; EOT (Week 24); and Safety Follow-up (Week 29) |
-2.0; -0.3; -2.3; 0.7; -1.0; 0.6 | — |
| SECONDARY Mean Columbia Suicide Severity Rating Scale (CSSRS) Scores at Screening; Baseline; Weeks 4, 8, 12, 16, and 20; EOT (Week 24); and Safety Follow-up (Week 29) |
0.0; 0.0; 0.0; 0.0; 0.0; 0.0 | — |
| SECONDARY Absolute Change From Baseline in the CSSRS Score at Weeks 4, 8, 12, 16, and 20; EOT (Week 24); and Safety Follow-up (Week 29) |
0.0; 0.0; 0.0; 0.0; 0.0; 0.0 | — |
| SECONDARY Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Screening, Baseline, and EOT (Week 24) |
130.8; 131.3; 122.8; 126.3; 122.4; 128.7 | — |
| SECONDARY Mean Heart Rate (HR) at Baseline, Screening, and EOT (Week 24) |
68.3; 74.0; 72.3; 75.2; 70.1; 74.7 | — |
| SECONDARY Mean Body Weight at Screening, Baseline ,and EOT (Week 24) |
89.3; 72.8; 89.6; 72.9; 88.9; 73.8 | — |
| SECONDARY Change From Baseline in SBP and DBP at EOT (Week 24) |
0.5; 0.7; -0.5; -4.2 | — |
| SECONDARY Change From Baseline in Heart Rate at EOT (Week 24) |
-3.1; -0.2 | — |
| SECONDARY Change From Baseline in Weight at EOT (Week 24) |
-0.8; -0.5 | — |
| SECONDARY Number of Participants With Normal/Abnormal Physical Status at Baseline With a Worst Post-Baseline Finding of Normal/Abnormal |
6; 18; 1; 0; 1; 1 | — |
| SECONDARY Number of Participants With a Negative Serum Pregnancy Test at Screening; Baseline; Weeks 4, 8, 12, 16, and 20; EOT (Week 24); and Safety Follow-up (Week 29) |
4; 7; 4; 7; 4; 4 | — |
Summary
The main purpose of this study is to demonstrate the improvement in the skin condition rate of patients receiving alitretinoin compared to patients receiving placebo.
Eligibility Criteria
Inclusion Criteria
- A female subject is eligible to participate if she is of:
- Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea and a follicle stimulating hormone concentration of ≥40 international units (IU)/L.
- Child-bearing potential with negative pregnancy test as determined by human chorionic gonadotropin (hCG) test at screening or prior to dosing and either 1) agrees to use a medically acceptable contraception method for an appropriate period of time (as determined by the product label or investigator) prior to the start of dosing to sufficiently minimize the risk of pregnancy at that point and continue contraception until the end of the study, or 2) has only same-sex partners, when this is her preferred and usual lifestyle.
- Capable of understanding and willing to provide signed and dated written voluntary informed consent (and any local or national authorization requirements) before any protocol specific procedures are performed.
- Male or female aged at least 18 years at time of consent and at time of first dose.
- Have PPP for at least 6 months, with or without psoriasis lesions on other areas of the skin
- A PPPASI score of at least 8 with involvement of at least 10% of the palms and/or the soles
- Refractory to standard topical corticosteroid therapy
Exclusion Criteria
- Unable to comply with the requirement of the study
- Female subjects who are pregnant or who plan to become pregnant or who are breast feeding
- Subjects whose disease is adequately controlled by standard non-medicated therapy (skin moisturizing and protection)
- Known hypersensitivity to other retinoids or vitamin A derivatives, or to any study medication component, especially soybean oil and partly hydrogenated soybean oil
- Treated with any of the following treatments 4 weeks before the start of study treatment:
- systemic drugs: corticosteroids, immunosuppressants, methotrexate
- phototherapy: ultraviolet B light therapy [UVB], psoralen with ultraviolet A combination therapy [PUVA], Grenz rays, X-rays
- Treated with biologic treatments within 6 weeks prior to start of study treatment.
- Abnormal hematology
- Treated with any systemic or topical retinoids within 3 months or 1 month, respectively, before start of study treatment
- Treated with high-potency topical corticosteroids within 2 weeks before the start of study treatment
- Severe generalized pustular psoriasis
- A skin condition of palms and/or soles that interferes with the diagnosis of PPP by the investigator
- Any condition that, in the judgment of the investigator, would put the subject at unacceptable risk for participation in the study.
- Hepatic insufficiency, severe renal failure, uncontrolled hypercholesterolemia as characterized by:
- AST/ ALT >2.5 x upper limit of normal (ULN)
- Creatinine clearance 1.5 x upper limit of normal (ULN)
- Fasting cholesterol >1.5 x ULN
- Fasting low-density lipoprotein (LDL) cholesterol >1.5x ULN
- Subjects with hypothyroidism as indicated by thyroid stimulating hormone (TSH) above ULN and thyroxine (T4) test below LLN or hypervitaminosis A
- Subjects with unstable cardiac disease or poorly controlled cardiovascular risk factors, for example:
- Acute coronary syndrome or coronary revascularization (percutaneous coronary intervention [PCI], coronary artery bypass graft [CABG]) within 3 months before start of study treatment
- Poorly controlled diabetes mellitus (HbA1c >8.5%)
- Systolic blood pressure ≥160 mm Hg and/or diastolic blood pressure ≥100 mm Hg at the screening examination
- Subjects receiving drugs with a potential for drug-drug interaction, such as systemic tetracyclines, ketoconazole, or St. John's Wort within 1 week, or receiving systemic itraconazole within 2 weeks, before start of study treatment
- Subjects included in the study of an investigational drug within 2
Data sourced from ClinicalTrials.gov (NCT01245140). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.