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Psoriasis-Type PsoriasisPhase 2NCT00521339

Apremilast Safety and PK Study in Recalcitrant Plaque Psoriasis

A Phase 2 study testing Apremilast in people with Psoriasis-Type Psoriasis and Plaque-Type Psoriasis, run by Amgen at 4 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The study will test the safety and tolerability of Apremilast twice a day in participants with recalcitrant plaque type psoriasis. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Apremilast
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
31 participants
Where
4 sitesUnited States
Study dates
1 Aug 2007to 1 May 2009
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Must understand and voluntarily sign an informed consent form
  • Must be male or female subject of any ethnic origin or race that is >18 years at time of consent
  • Must have a documented history of plaque-type psoriasis for at least 6 months prior to screening visit
  • Subjects must fulfill criteria outlined in at least one of the following clinical categories:
  • Unresponsive to standard systemic therapy, as defined by clinical history, in the investigator's opinion, i.e. inadequate response to one or more adequate treatment course (s) of standard systemic therapy
  • Intolerant to or cannot receive (e.g., contraindication to prescribe) standard systemic therapy or biological interventions for psoriasis
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  • Must have a Static Physician Global Assessment (sPGA) score of at least 3 and a Body surface area (BSA) ≥ 10% at screening
  • Must meet the specified laboratory criteria:
  • o Must be able to adhere to the study visit schedule and study protocol requirements
  • Females of childbearing potential (FCBP) must have a negative urine pregnancy test at screening (Visit 1). In addition, FCBP must agree to use two of the following adequate forms of contraception methods such as oral, injectable, or implantable hormonal contraception; tubal ligation; intrauterine device; barrier contraceptive with spermicide or vasectomized partner while on study. A FCBP must agree to have pregnancy tests every 4 weeks while on study medication.
  • Males (including those who have had a vasectomy) must agree to use barrier contraception (latex condoms) when engaging in sexual activity with FCBP

Who cannot join

  • History of clinically significant (as determined by the investigator) cardiac, endocrinologic, pulmonary, neurologic, psychiatric, hepatic, renal, hematologic, immunologic, or other major disease
  • Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study
  • Pregnant or lactating females
  • History of active tuberculosis (TB) infection within 3 years prior to the screening visit. Infections which occurred > 3 years prior to entry must have been effectively treated
  • History of incompletely treated latent (as indicated by a positive PPD [purified protein derivative] skin results) TB infection
  • Clinically significant abnormality on the chest x-ray (CXR) at screening
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  • Psoriasis flare within 30 days of screening, as defined by protocol
  • Use of systemic therapy for psoriasis within 28 days of Visit 2 (Baseline).
  • Topical therapy as defined in the protocol Adalimumab, etanercept, efalizumab or infliximab use within 56 days of Visit 2 (Baseline)
  • Alefacept use within 180 days of Visit 2 (Baseline)
  • Phototherapy Ultraviolet light A (UVA), Ultraviolet light B (UVB), Psoralens and long-wave ultraviolet radiation (PUVA) within 28 days of Visit 2 (Baseline)
  • Use of any investigational drug within 28 days of Visit 2 (Baseline), or 5 half lives if known (whichever is longer) Clinically significant abnormality on 12-lead Electrocardiogram (ECG) at screening

Trial locations and contacts

4 sites in 1 country.

United States4 sites

  • Tufts-New England Medical Center Hospitals

    Boston, Massachusetts, 02111

  • Baylor Research Institute

    Dallas, Texas, 75246-1613

  • Oregon Medical Research Center, P.C.

    Portland, Oregon, 97223

  • Central Dermatology

    St Louis, Missouri, 63117

Other trials in United States

About this study

Official title: A Phase 2, Open-label Multi-center Study to Evaluate the Safety, Pharmacodynamics, Pharmacokinetics, and Efficacy of Apremilast in Subjects With Recalcitrant Plaque-type Psoriasis

The study will test the safety and tolerability of Apremilast twice a day in participants with recalcitrant plaque type psoriasis.

Read the detailed description

This is a phase 2, multicenter, open-label, study to evaluate the safety, tolerability, pharmacodynamics, pharmacokinetics and efficacy of Apremilast in participants with recalcitrant plaque-type psoriasis.

Approximately 31 participants were enrolled and received 20 mg apremilast orally BID and, in participants who are non-responders after 84 days of apremilast, 30 mg Apremilast over the course of the two study treatment phases. The study consisted of four phases: Screening Phase - up to 35 days, Treatment Phase of 84 days, Extension Phase of 84 days and a Observational Follow-up Phase of 28 days.

During the Treatment Phase, participants received two 20 mg Apremilast capsules each day. Following the Treatment Phase, participants had the option to continue on treatment during the Extension Phase. During the Extension Phase, participants either continued to take two 20 mg or dose escalated to two 30 mg of Apremilast each day. Participants who were considered responders (achieved a Psoriasis Area and Severity Index (PASI-75) at the beginning of the Extension Phase continued on 20 mg twice per day (BID) while the remaining participants received 30 mg capsules BID. The Extension Phase was introduced after some participants had already completed the study; therefore, there were several participants who never had the opportunity to continue into the Extension Phase. All participants were asked to participate in a 4-week post-treatment observational follow-up phase either upon completion of the study or upon discontinuation of study drug for those participants who terminated the study early.

Being tested
Apremilast
Keywords
Apremilast,, Psoriasis,, PASI-75,, sPGA
Medical subject headings
Psoriasis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ApremilastDrug

    Also called Otezla, CC-10004

    20 mg PO (by mouth) twice per day (BID) for 84 days and then an additional 84 days during the optional treatment extension period. For subjects meeting the dose escalation criteria, dosage during the optional treatment extension period can be increased to 30 mg BID.

Study groups in NCT00521339
Study groupRoleWhat they receive
Apremilast 20 mg BID/ 30 mg BIDExperimentalApremilast 20 mg or 30 mg orally twice per day
Receives: Drug: Apremilast

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Treatment Emergent Adverse Events (TEAEs) During the Treatment Phase

    TEAE = any AE occurring or worsening on or after the first treatment with any study drug. Related = suspected by investigator to be related to study treatment. National Cancer Institute [NCI] Common Toxicity Criteria for Adverse Events [CTCAE], Version 3.0, grades: 1 = mild, 2 = moderate, 3 = severe, 4 = life threatening, 5 = death.

    Adverse event (AE) = any noxious, unintended, or untoward medical occurrence occurring at any dose that may appear or worsen in a participant during the course of a study, including new intercurrent illness, worsening concomitant illness, injury, or any concomitant impairment of participant's health, including laboratory test values, regardless of etiology. Serious adverse event (SAE) = any AE which results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect; constitutes an important medical event.

    Measured: Week 0 to Week 12

  2. Treatment Emergent Adverse Events (TEAEs) During the Extension Phase

    TEAE = any AE occurring or worsening on or after the first treatment with any study drug. Related = suspected by investigator to be related to study treatment. National Cancer Institute [NCI] Common Toxicity Criteria for Adverse Events [CTCAE], Version 3.0, grades: 1 = mild, 2 = moderate, 3 = severe, 4 = life threatening, 5 = death.

    Adverse event (AE) = any noxious, unintended, or untoward medical occurrence occurring at any dose that may appear or worsen in a participant during the course of a study, including new intercurrent illness, worsening concomitant illness, injury, or any concomitant impairment of participant's health, including laboratory test values, regardless of etiology. Serious adverse event (SAE) = any AE which: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; constitutes an important medical event.

    Measured: Week 12 to Week 24

Secondary outcomes (55)

  1. Percentage of Participants With at Least a 1 Point Reduction on 0 to 5 Point Scale From Baseline in Static Physician Global Assessment (sPGA) at Week 12

    The static Physician's Global Assessment (sPGA) rated the investigator's overall clinical assessment of a participants plaque thickness, erythema, and scaling on a 6-point scale ranging from 0 (clear, except for residual discoloration) to 5 (majority of plaques have severe thickness, erythema, and scale). To assign a sPGA score, the investigator examined all psoriatic lesions and assigned a severity score ranging from 0 to 5 for thickness, erythema, and scaling. Scores for thickness, erythema, and scaling are summed and the mean of these 3 scores equals the overall sPGA score. Decreases in sPGA correspond to clinical improvement.

    Measured: Baseline and Week 12

  2. Percent Change From Baseline in Psoriasis Area Severity Index (PASI) Score at Week 12

    The PASI score was a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness, and scaling) and degree of skin surface area involvement on defined anatomical regions. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement). The total qualitative score (sum of erythema, thickness, and scaling scores) was multiplied by the degree of involvement for each anatomic region and then multiplied by a constant. These values for each anatomic region are summed to yield the PASI score.

    Measured: Baseline and Week 12

  3. Percentage of Participants Who Achieved a PASI-75 Score at Week 12

    PASI-75 response is the percentage of participants who achieved at least a 75% reduction (improvement) from baseline in PASI score at Week 12. The improvement in PASI score was used as a measure of efficacy. The PASI was a measure of psoriatic disease severity taking into account qualitative lesion characteristics and degree of skin surface area involvement on defined anatomical regions. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the4 anatomic regions was scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement). The total qualitative score (sum of erythema, thickness, and scaling scores) was multiplied by the degree of involvement for each anatomic region and then multiplied by a constant.

    Measured: Baseline to Week 12

  4. Percentage of Participants Who Achieved a PASI-50 Score at Week 12

    PASI -50 response is the percentage of participants who achieved at least a 50% reduction (improvement) from baseline in PASI score at Week 12. The improvement in PASI score was used as a measure of efficacy. The PASI was a measure of psoriatic disease severity taking into account qualitative lesion characteristics and degree of skin surface area involvement on defined anatomical regions. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head,trunk, upper limbs, and lower limbs. Degree of involvement on each of the4 anatomic regions was scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement). The total qualitative score (sum of erythema, thickness, and scaling scores) was multiplied by the degree of involvement for each anatomic region and then multiplied by a constant.

    Measured: Baseline to Week 12

  5. Maximal PASI Response Documented for Each Participant During Treatment Phase

    PASI was a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness and scaling) and degree of skin surface area involvement on defined anatomical regions. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head,trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement). The total qualitative score (sum of erythema, thickness, and scaling scores) is multiplied by the degree of involvement for each anatomic region and then multiplied by a constant. These values for each anatomic region are summed to yield the PASI score.

    Measured: Baseline to Week 12

  6. Percent Change From Baseline in the Psoriasis Affected Body Surface Area (BSA) Involvement at Week 12

    The BSA estimate was based on the palm area of the hand of the participant which equates to 1% of the total body surface area.

    Measured: Baseline to Week 12

  7. Time to Clinically Relevant Response (Time to Achieve PASI-50) During Treatment Phase

    Time to clinically relevant response (time to achieve PASI-50) during treatment phase was not analyzed. The PASI was a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness, and scaling) and degree of skin surface area involvement on defined anatomical regions. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head,trunk, upper limbs, and lower limbs. Degree of involvement on each of the4 anatomic regions was scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement). The total qualitative score (sum of erythema, thickness, and scaling scores) was multiplied by the degree of involvement for each anatomic region and then multiplied by a constant. These values for each anatomic region are summed to yield the PASI score.

  8. Time to Achieve PASI-75 During Treatment Phase

    Time to achieve PASI-75 during treatment phase was not analyzed. The PASI was a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness, and scaling) and degree of skin surface area involvement on defined anatomical regions. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the4 anatomic regions was scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement). The total qualitative score (sum of erythema, thickness, and scaling scores) was multiplied by the degree of involvement for each anatomic region and then multiplied by a constant. These values for each anatomic region are summed to yield the PASI score.

  9. Time to Relapse of Psoriasis (50% Loss of Maximal PASI Score Improvement in Participants Who Achieved at Least PASI-50 During the Treatment Phase) During the Observational Follow up Phase

    Time to relapse of psoriasis (50% loss of maximal PASI score improvement in participants who achieved at least PASI-50 during the treatment phase) during the observational follow up phase was not analyzed. Time to relapse of psoriasis was defined as a 50% loss of maximal PASI score improvement in participants who achieved at least PASI-50 during the treatment or extension phase. The lesion on each area of the body was assessed for redness, thickness, and scaling.

    Measured: 28-day Observational Follow-up Phase; Days 168 to Day 196.

  10. Percent of Participants With Psoriatic Arthritis Who Achieved an American College of Rheumatology 20% Improvement (ACR-20) Response at Week 12

    A participant was a responder if the following 3 criteria for improvement from baseline were met:

    • ≥ 20% improvement in 78 tender joint count;
    • ≥ 20% improvement in 76 swollen joint count; and
    • ≥ 20% improvement in at least 3 of the 5 following parameters: Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]); Patient's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); C-Reactive Protein.

    Measured: Baseline to Week 12

  11. Time to Relapse of Psoriatic Arthritis During the Observational Follow-up Phase

    A relapse was defined as a 50% loss of maximal American College of Rheumatoid (ACR) Score improvement in participants with psoriatic arthritis who achieved at least an ACR 20 score during the treatment phase.

    Relapses were only captured prior to the prescription of concomitant psoriatic treatment.

    Measured: Observational follow up phase; Days 168 to Day 196

  12. Area Under the Plasma Concentration Time-curve From 0 to 12 Hours Post Dose (AUC 0-12)

    Plasma concentrations of apremilast were determined using validated chiral liquid chromatography-mass spectrometry methods (LC-MS/MS). For Day 1, AUC0-12 was calculated, using linear trapezoidal area method in WinNonlin (linear-linear trapezoidal). For Days 85 and 169/170, the AUC during a dosing interval (12 hours) (AUC0-12), was calculated at steady-state using the partial area function within WinNonlin.

    .

    Measured: Day 85 Pre-dose, 0.5, 1, 2, 4, 8, and 12 hours after the AM dose

  13. Peak (Maximum) Plasma Concentration of Medication (Cmax)

    The maximum observed plasma concentration of apremilast (Cmax); the maximum plasma concentration (Cmax) was obtained directly from the observed concentration-time data on Days 1, 85, and 169/170, respectively.

    Measured: Day 85 Pre-dose, 0.5, 1, 2, 4, 8, and 12 hours after the AM dose

  14. Trough Plasma Concentration (Cmin)

    The trough observed plasma concentration of apremilast (Cmin) was determined directly from the observed pre-AM dose concentration on Day 85.

    Measured: Day 85 Pre-dose

  15. Time to Maximum Plasma Concentration (Tmax) During the Treatment Phase

    The time to reach Cmax (Tmax) was obtained directly from the observed concentration-time data on Day 85. Actual times utilized were used for reporting Tmax values.

    Measured: Day 85 Pre-dose, 0.5, 1, 2, 4, 8, and 12 hours after the AM dose

  16. Terminal Phase Elimination Half Life of Apremilast (t½)

    Terminal phase elimination half-life (t1/2) was calculated as follows: t1/2 = 0.693/λz. The terminal elimination rate constant (λZ) was estimated by linear regression of the log-transformed concentration-time data.

    Measured: Day 85 Pre-dose, 0.5, 1, 2, 4, 8, and 12 hours after the AM dose

  17. Apparent Total Clearance of Apremilast From Plasma After Extravascular Administration (CLz/F) During the Treatment Phase

    The apparent total clearance of apremilast from plasma after extravascular administration (CLz/F); for Day 1, apparent clearance of drug from plasma (CL/F) was not calculated.

    For Day 85, Apparent clearance of drug from plasma after extravascular administration (CL/F) was calculated as follows: CL/F= Dose/AUC^12 where τ=12.

    Measured: Day 85 Pre-dose, 0.5, 1, 2, 4, 8, and 12 hours after the AM dose

  18. Apparent Total Volume of Distribution During the Terminal Phase After Extravascular Administration (Vz/F) During the Treatment Phase

    Apparent volume of distribution during the terminal phase after extravascular administration (Vz/F) (for Days 1, 85, and 169/170)

    1. For Day 1, Vz/F was not calculated.
    2. For Days 85 and 169/170, apparent volume of distribution of drug (V/z) based on the terminal phase was calculated as follows: Vz/F=Dose/(λ*AUC^12)

    Measured: Day 85

  19. Accumulation Index (R)

    Accumulation represents the relationship between the dosing interval and the rate of elimination for the drug.

    Measured: Day 85 Pre-dose, 0.5, 1, 2, 4, 8, and 12 hours after the AM dose

  20. Mean Residence Time (MRT) During the Treatment Phase

    Mean Residence Time (MRT) is defined as the mean duration of time the drug spends in the body. The average concentration at steady state (Cavg) (for Day 85 was calculated as follows: Cavg = (Day 85 AUC0-12)/(12).

    Measured: Day 85 Pre-dose, 0.5, 1, 2, 4, 8, and 12 hours after the AM dose

  21. Change From Baseline in Peripheral Blood T Cell, B Cell, and NK Cell Subsets at Week 12

    T cells or T lymphocytes, a type of white blood cell, play a role in cell-mediated immunity. T cells are distinguished from other lymphocytes by the presence of a T-cell receptor (TCR) on the cell surface and mature in the thymus. B cells, a type of lymphocyte in the humoral immunity of the adaptive immune system can be distinguished by the presence of a protein on the B cells outer surface called a B cell receptor (BCR). This receptor protein allows a B cell to bind to a specific antigen and make antibodies against antigens [(antigen-presenting cells APCs)], and to develop into memory B cells after activation by antigen interaction. Natural Killer Cells (NK) are a type of cytotoxic lymphocyte critical to the innate immune system. Their role is analogous to that of cytotoxic T cells in the vertebrate adaptive immune response. They constitute the third kind of cells differentiated from the common lymphoid progenitor generating B and T lymphocytes and mature in the bone marrow.

    Measured: Baseline and Week 12

  22. Percent Change From Baseline of CD3 in the Dermis of the Psoriatic Skin Biopsy at Week 12

    The aim of the study was to measure the pharmacodynamic effects of apremilast in participants with plaque psoriasis in skin affected by psoriasis, immune cells enter the skin through blood vessels and cause the epidermis to grow very rapidly and to stop shedding properly. This causes thickening of the skin as well as the scaly build up composed of dead skin cells seen on areas affected by psoriasis.

    Measured: Baseline and Week 12

  23. Percent Change From Baseline of CD3 in the Epidermis of the Psoriatic Skin Biopsy at Week 12

    The aim of the study was to measure the pharmacodynamic effects of apremilast in participants with plaque psoriasis in skin affected by psoriasis, immune cells enter the skin through blood vessels and cause the epidermis to grow very rapidly and to stop shedding properly. This causes thickening of the skin as well as the scaly build up composed of dead skin cells seen on areas affected by psoriasis.

    Measured: Baseline and Week 12

  24. Percent Change From Baseline of CD 11c in the Dermis of the Psoriatic Skin Biopsy at Week 12

    The aim of the study was to measure the pharmacodynamic effects of apremilast in participants with plaque psoriasis in skin affected by psoriasis, immune cells enter the skin through blood vessels and cause the epidermis to grow very rapidly and to stop shedding properly. This causes thickening of the skin as well as the scaly build up composed of dead skin cells seen on areas affected by psoriasis.

    Measured: Baseline and Week 12

  25. Percent Change From Baseline of CD11c in the Epidermis of the Psoriatic Skin Biopsy at Week 12

    The aim of the study was to measure the pharmacodynamic effects of apremilast in participants with plaque psoriasis in skin affected by psoriasis, immune cells enter the skin through blood vessels and cause the epidermis to grow very rapidly and to stop shedding properly. This causes thickening of the skin as well as the scaly build up composed of dead skin cells seen on areas affected by psoriasis.

    Measured: Baseline and Week 12

  26. Percent Change From Baseline of CD56 in the Dermis of the Psoriatic Skin Biopsy at Week 12

    The aim of the study was to measure the pharmacodynamic effects of apremilast in participants with plaque psoriasis in skin affected by psoriasis, immune cells enter the skin through blood vessels and cause the epidermis to grow very rapidly and to stop shedding properly. This causes thickening of the skin as well as the scaly build up composed of dead skin cells seen on areas affected by psoriasis.

    Measured: Baseline and Week 12

  27. Percent Change From Baseline of CD56 in the Epidermis of the Psoriatic Skin Biopsy at Week 12

    The aim of the study was to measure the pharmacodynamic effects of apremilast in participants with plaque psoriasis in skin affected by psoriasis, immune cells enter the skin through blood vessels and cause the epidermis to grow very rapidly and to stop shedding properly. This causes thickening of the skin as well as the scaly build up composed of dead skin cells seen on areas affected by psoriasis.

    Measured: Baseline and Week 12

  28. Percent Change From Baseline of Langerin in the Dermis of Psoriatic Skin Biopsy at Week 12

    The aim of the study was to measure the pharmacodynamic effects of apremilast in participants with plaque psoriasis in skin affected by psoriasis, immune cells enter the skin through blood vessels and cause the epidermis to grow very rapidly and to stop shedding properly. This causes thickening of the skin as well as the scaly build up composed of dead skin cells seen on areas affected by psoriasis.

    Measured: Baseline and Week 12

  29. Percent Change From Baseline of Langerin in the Epidermis of the Psoriatic Skin Biopsy at Week 12

    The aim of the study was to measure the pharmacodynamic effects of apremilast in participants with plaque psoriasis in skin affected by psoriasis, immune cells enter the skin through blood vessels and cause the epidermis to grow very rapidly and to stop shedding properly. This causes thickening of the skin as well as the scaly build up composed of dead skin cells seen on areas affected by psoriasis.

    Measured: Baseline and Week 12

  30. Percent Change From Baseline of Epidermal Thickness in the Psoriatic Skin Biopsy at Week 12

    The aim of the study was to measure the pharmacodynamic effects of apremilast in participants with plaque psoriasis in skin affected by psoriasis, immune cells enter the skin through blood vessels and cause the epidermis to grow very rapidly and to stop shedding properly. This causes thickening of the skin as well as the scaly build up composed of dead skin cells seen on areas affected by psoriasis.

    Measured: Baseline and Week 12

  31. Percent Change From Baseline in the Inducible Nitric Oxide (iNOS) Inflammatory Marker in Psoriatic Skin Biopsies

    Inflammatory markers associated with psoriasis (using skin biopsies) were used to detect acute inflammation and as markers of treatment response. The inflammatory markers were measured using Reverse transcriptase polymerase chain reaction (RT-PCR) and the messenger Ribonucleic acid (mRNA) is being measured.

    Measured: Baseline and Week 12

  32. Percent Change From Baseline in the Interleukin (IL) IL-22 Inflammatory Marker in Psoriatic Skin Biopsies

    Inflammatory markers associated with psoriasis (using skin biopsies) were used to detect acute inflammation and as markers of treatment response. The inflammatory markers were measured using Reverse transcriptase polymerase chain reaction (RT-PCR) and the messenger Ribonucleic acid (mRNA) is being measured.

    Measured: Baseline and Week 12

  33. Percent Change From Baseline in the p40 Inflammatory Marker in Psoriatic Skin Biopsies

    Inflammatory markers associated with psoriasis (using skin biopsies) were used to detect acute inflammation and as markers of treatment response. The inflammatory markers were measured using Reverse transcriptase polymerase chain reaction (RT-PCR) and the messenger Ribonucleic acid (mRNA) is being measured.

    Measured: Baseline and Week 12

  34. Percent Change From Baseline in the Defensin Beta 4 (DEFB4) Inflammatory Marker in Psoriatic Skin Biopsies

    Inflammatory markers associated with psoriasis (using skin biopsies) were used to detect acute inflammation and as markers of treatment response. The inflammatory markers were measured using Reverse transcriptase polymerase chain reaction (RT-PCR) and the messenger Ribonucleic acid (mRNA) i being measured.

    Measured: Baseline and Week 12

  35. Percent Change From Baseline in the keratin16 (K16) Inflammatory Marker in Psoriatic Skin Biopsies

    Inflammatory markers associated with psoriasis (using skin biopsies) were used to detect acute inflammation and as markers of treatment response. The inflammatory markers were measured using Reverse transcriptase polymerase chain reaction (RT-PCR) and the messenger Ribonucleic acid (mRNA) is being measured.

    Measured: Baseline and Week 12

  36. Percent Change From Baseline in the pluripotent19 (P19) Inflammatory Marker in Psoriatic Skin Biopsies

    Inflammatory markers associated with psoriasis (using skin biopsies) were used to detect acute inflammation and as markers of treatment response. The inflammatory markers were measured using Reverse transcriptase polymerase chain reaction (RT-PCR) and the messenger Ribonucleic acid (mRNA) is being measured.

    Measured: Baseline and Week 12

  37. Percent Change From Baseline in the IL8 Inflammatory Marker in Psoriatic Skin Biopsies

    Inflammatory markers associated with psoriasis (using skin biopsies) were used to detect acute inflammation and as markers of treatment response. The inflammatory markers were measured using Reverse transcriptase polymerase chain reaction (RT-PCR) and the messenger Ribonucleic acid (mRNA) is being measured.

    Measured: Baseline and Week 12

  38. Percent Change From Baseline in the MX1 (Gene That Encodes the Interferon-induced p78 Protein) Inflammatory Marker in Psoriatic Skin Biopsies

    Inflammatory markers associated with psoriasis (using skin biopsies) were used to detect acute inflammation and as markers of treatment response. The inflammatory markers were measured using Reverse transcriptase polymerase chain reaction (RT-PCR) and the messenger Ribonucleic acid (mRNA) is being measured.

    Measured: Baseline and Week 12

  39. Percent Change From Baseline in the IL17A Inflammatory Marker in Psoriatic Skin Biopsies

    Inflammatory markers associated with psoriasis (using skin biopsies) were used to detect acute inflammation and as markers of treatment response. The inflammatory markers were measured using Reverse transcriptase polymerase chain reaction (RT-PCR) and the messenger Ribonucleic acid (mRNA) is being measured.

    Measured: Baseline and Week 12

  40. Percent Change From Baseline in the Tumor Necrosing Factor (TNF) Alpha Inflammatory Marker in Psoriatic Skin Biopsies

    Inflammatory markers associated with psoriasis (using skin biopsies) were used to detect acute inflammation and as markers of treatment response. The inflammatory markers were measured using Reverse transcriptase polymerase chain reaction (RT-PCR) and the messenger Ribonucleic acid (mRNA) is being measured.

    Measured: Week 0 to Week 12

  41. Percent Change From Baseline in the Interferon (INF) Gamma Inflammatory Marker in Psoriatic Skin Biopsies

    Inflammatory markers associated with psoriasis (using skin biopsies) were used to detect acute inflammation and as markers of treatment response. The inflammatory markers were measured using Reverse transcriptase polymerase chain reaction (RT-PCR) and the messenger Ribonucleic acid (mRNA) is being measured.

    Measured: Baseline and Week 12

  42. Percent Change From Baseline in the IL10 Inflammatory Marker in Psoriatic Skin Biopsies

    Inflammatory markers associated with psoriasis (using skin biopsies) were used to detect acute inflammation and as markers of treatment response. The inflammatory markers were measured using Reverse transcriptase polymerase chain reaction (RT-PCR) and the messenger Ribonucleic acid (mRNA) is being measured.

    Measured: Baseline and Week 12

  43. Percent Change From Baseline in the Chemokine Ligand (CXCL9) Inflammatory Marker in Psoriatic Skin Biopsies

    Inflammatory markers associated with psoriasis (using skin biopsies) were used to detect acute inflammation and as markers of treatment response. The inflammatory markers were measured using Reverse transcriptase polymerase chain reaction (RT-PCR) and the messenger Ribonucleic acid (mRNA) is being measured.

    Measured: Baseline and Week 12

  44. Percent Change From Baseline in the IL2 Inflammatory Marker in Psoriatic Skin Biopsies

    Inflammatory markers associated with psoriasis (using skin biopsies) were used to detect acute inflammation and as markers of treatment response. The inflammatory markers were measured using Reverse transcriptase polymerase chain reaction (RT-PCR) and the messenger Ribonucleic acid (mRNA) is being measured.

    Measured: Baseline and Week 12

  45. Percent Change From Baseline in the Dendritic Cell (CD83) Inflammatory Marker in Psoriatic Skin Biopsies

    Inflammatory markers associated with psoriasis (using skin biopsies) were used to detect acute inflammation and as markers of treatment response. The inflammatory markers were measured using Reverse transcriptase polymerase chain reaction (RT-PCR) and the messenger Ribonucleic acid (mRNA) is being measured.

    Measured: Baseline and Week 12

  46. Change From Baseline in the Dermatology Life Quality Index (DLQI) at Week 12

    DLQI was the dermatology-specific quality of life (QOL) measure used for the psoriatic population. The DLQI was a validated, self-administered, 10-item questionnaire that measures the impact of skin disease on a participants QoL, based on recall over the past week. Domains include symptoms, feelings, daily activities, leisure, work, personal relationships, and treatment. Possible responses for each of the 10 items are: not at all, a little, a lot, and very much. Each question is rated on a scale of 0 to 3 with a total range of 0 to 30. Higher scores indicate greater impact of disease on QOL

    Measured: Baseline to Week 12

  47. Change From Baseline in the Medical Outcome Study Short Form 36-item Health Survey (SF-36) Scores, Mental and Physical Components to Week 12

    The SF-36 was a self-administered instrument consisting of 8 multi-item scales that assess 8 health domains: 1) limitations in physical activities because of health problems; 2) limitations in social activities because of physical or emotional problems; 3) limitations in usual role activities because of physical health problems; 4) bodily pain; 5) general mental health (psychological distress and well-being); 6) limitations in usual role activities because of emotional problems; 7) vitality (energy and fatigue); and 8) general health perceptions. A higher score post-baseline is indicative of improvement in the disease state. The summary physical health score included physical functioning, role-physical, bodily pain and general health. The summary mental health score included: vitality, social functioning, role-emotional and mental health. The resulting score for each subscale is then standardized, to obtain values ranging from 0 to 100, with higher values indicating a better QOL.

    Measured: Baseline to Week 12

  48. Area Under the Plasma Concentration Time-curve From 0 to 12 Hours Post Dose (AUC 0-12) During the Extension Phase

    Plasma concentrations of apremilast were determined using validated chiral liquid chromatography-mass spectrometry methods (LC-MS/MS).

    Measured: Day 169 pre-dose, 0.5, 1, 2, 4, 8 12, 24 and 36 hours after AM dose

  49. Peak (Maximum) Plasma Concentration of Apremilast (Cmax) During the Extension Phase

    The maximum observed plasma concentration of CC-10004 (Cmax); the maximum plasma concentration (Cmax) was obtained directly from the observed concentration-time data on Days 169/170.

    Measured: Day 169 pre-dose, 0.5, 1, 2, 4, 8 12, 24 and 36 hours after AM dose

  50. Time to Maximum Plasma Concentration (Tmax) During the Extension Phase

    The time to reach Cmax (Tmax) was obtained directly from the observed concentration-time data on Day 169/170. Actual times utilized were used for reporting Tmax values.

    Measured: Day 169 pre-dose, 0.5, 1, 2, 4, 8 12, 24 and 36 hours after AM dose

  51. Terminal Phase Elimination Half Life of Apremilast (t½) During the Extension Phase

    Terminal phase elimination half-life (t1/2) was calculated as follows: t1/2 = 0.693/λz. The terminal elimination rate constant (λZ) was estimated by linear regression of the log-transformed concentration-time data.

    Measured: Day 169 pre-dose, 0.5, 1, 2, 4, 8 12, 24 and 36 hours after AM dose

  52. Apparent Total Clearance of Apremilast From Plasma After Extravascular Administration (CL/F) During the Extension Phase

    For 169/170, apparent clearance of drug from plasma after extravascular administration (CL/F) was calculated as follows: CL/F= Dose/AUC12

    Measured: Day 169 pre-dose, 0.5, 1, 2, 4, 8 12, 24 and 36 hours after AM dose

  53. Apparent Total Volume of Distribution During the Terminal Phase After Extravascular Administration (Vz/F) During the Extension Phase

    For Days 169/170, apparent volume of distribution of drug (V/z) based on the terminal phase was calculated as follows: Vz/F=Dose/(λ*AUC12) where λ = the terminal elimination rate constant

    Measured: Day 169 pre-dose, 0.5, 1, 2, 4, 8 12, 24 and 36 hours after AM dose

  54. Accumulation Index During the Extension Phase

    Accumulation represents the relationship between the dosing interval and the rate of elimination for the drug.

    Measured: Day 169 pre-dose, 0.5, 1, 2, 4, 8 12, 24 and 36 hours after AM dose

  55. Mean Residence Time (MRT) During the Extension Phase

    Mean Residence Time (MRT) is defined as the mean duration of time the drug spends in the body. The average concentration at steady state (Cavg) (for Days169/170) was calculated as follows: Cavg = (Day 169/170)/(12)

    Measured: Day 169 pre-dose, 0.5, 1, 2, 4, 8 12, 24 and 36 hours after AM dose

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Aug 2007 (estimated)
  2. Study start1 Aug 2007
  3. Primary completion1 Apr 2009
  4. Study completion1 May 2009

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
31 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00521339
Sponsor's protocol ID
CC-10004-PSOR-004
Status last verified
Apr 2020
First submitted
24 Aug 2007
Last updated
7 May 2020
Data monitoring committee
Yes

Publications

  • Gottlieb AB, Matheson RT, Menter A, Leonardi CL, Day RM, Hu C, Schafer PH, Krueger JG. Efficacy, tolerability, and pharmacodynamics of apremilast in recalcitrant plaque psoriasis: a phase II open-label study. J Drugs Dermatol. 2013 Aug;12(8):888-97.

    PubMed 23986162

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Apremilast in people with Psoriasis-Type Psoriasis and Plaque-Type Psoriasis, run by Amgen at 4 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 7 May 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 27 May 2010). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Treatment Emergent Adverse Events (TEAEs) During the Treatment Phase (time frame: Week 0 to Week 12). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00521339, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 May 2020.

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