Open Label Pilot Study of Apremilast in Treatment of Rosacea
Condition: Erythematotelangiectatic Rosacea; Papulopustular Rosacea
MeSH terms: Rosacea
Intervention: Apremilast
Intervention description: 20mg taken orally twice per day for 12 weeks
Intervention MeSH terms: Apremilast
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 10.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Inflammatory rosacea; Papules and pustules; Moderate to severe erythema; Telangiectasia

Summary:

      Rosacea is a chronic skin disorder with the signs and symptoms of facial flushing, persistent
      redness, small visible spider-like veins, papules (inflamed red bumps under the skin) and
      pustules. Rosacea is also a a recurring skin disorder. In addition to causing uncomfortable
      and embarrassing physical symptoms such as flushing, burning, and itching, rosacea can also
      contribute to lower self-esteem, which can have a significant psychosocial impact on quality
      of life. Rosacea flares can be triggered by every day factors such as sun exposure, heat, hot
      or caffeinated drinks, alcoholic beverages, spices and stress.

      Many of the currently available treatments for rosacea are only partially effective and some
      patients do not respond to them, or are unable to tolerate the side effects.

      This is a single-center, open label trial of Apremilast in ten (10) subjects with moderate to
      severe inflammatory rosacea who will be treated with Apremilast 20 mg twice per day for 12
      weeks. Following the screening period and baseline visit, study subjects will return at weeks
      1, 2, 4, 6, 8, 10 and 12. There is a follow up study visit at week 16.

      Recent research has shown an increase of specific proinflammatory cytokines in the biopsies
      of inflammatory lesions from rosacea and acne patients. The cytokines then trigger a chain of
      chemical responses in the body that likely result in the development of the papules an
      pustules that are seen in rosacea and acne patients. Apremilast is an oral agent that
      modulates multiple anti-inflammatory pathways and has pharmacodynamic properties with
      potential therapeutic benefit for treating inflammatory autoimmune disorders.

      The investigators therefore propose a pilot study to evaluate the potential for Apremilast to
      improve the signs and symptoms of moderate to severe inflammatory rosacea.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Must be a healthy, post-pubescent male or female 18 years of age or older with
             moderate to severe erythematotelangiectatic and papulopustular rosacea, defined as 10
             to 40 papules and pustules

          -  Must have presence of moderate to severe erythema

          -  Must have presence of telangiectasia

          -  Must have a diagnosis or findings consistent with a diagnosis of
             erythematotelangiectatic rosacea and papulopustular rosacea

          -  Must understand and voluntarily sign an informed consent form

          -  Must be ale to adhere to the study visit schedule and other protocol requirements

          -  Must be able to restrict diet in order to avoid foods/drinks that are known triggers
             that would exacerbate the signs/symptoms of rosacea

          -  Must have within normal range for routine blood laboratory tests

          -  Females of childbearing potential must have a negative urine pregnancy test at
             screening and if sexually active must agree to use two(2) forms of contraception
             (adequate forms of contraception are outlined in the protocol)

          -  Females of childbearing potential must agree to serum 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 females of
             childbearing potential while on study medication and for 84 days after taking the last
             dose of study medication

        Exclusion Criteria:

          -  Inability to provide voluntary consent

          -  Diagnosis of acne vulgaris or perioral dermatitis

          -  Use of topical acne or rosacea treatments within 4 weeks of baseline

          -  Use of systemic retinoids within 90 days of baseline

          -  Known or suspected excessive alcohol intake (which in the opinion of the investigator
             will exacerbate the signs and symptoms of rosacea)

          -  Use of any investigational medication within 4 weeks prior to start of study drug or 5
             pharmacokinetic/pharmacodynamic half-lives (whichever is longer)

          -  A known sensitivity to tetracyclines

          -  Currently taking clinically significant concomitant drug therapy

          -  Use of any acne or rosacea treatment during the course of the study or within four
             weeks of starting the study medication, including azelaic acid, topical or systemic
             retinoids, sulfa drugs, erythromycin, cephalosporins, quinolones, tetracycline,
             benzoyl peroxide products, as well as pulse dye laser, intense pulsed light and
             photodynamic therapy

          -  Current use and inability to discontinue use of PDE 4 inhibitors, theophylline,
             systemic steroids (oral or inhaled), penicillin antibiotics, niacin greater than 500
             mg/day, chronic use of NSAIDS, or use of any medication that in the opinion of the
             investigator affects the severity of rosacea

          -  Long-term use (greater than 14 days) of topical or systemic anti-inflammatories in the
             4 weeks prior to baseline and during the study. Chronic use of aspirin at
             sub-analgesic doses (less than 325 mg once daily) is acceptable for patients requiring
             platelet aggregation inhibition

          -  Use of topical or systemic corticosteroids 4 weeks prior to baseline and during the
             study

          -  Patients with ocular rosacea and/or blepharitis/meibomianitis who required treatment
             by an ophthalmologist

          -  Patients who had surgeries that bypassed or excluded the duodenum

          -  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 breastfeeding women, or women of childbearing potential who are not using
             an adequate form of birth control as described in the inclusion criteria

          -  Initiation of a hormonal method of birth contraception within 4 months of baseline,
             discontinuation during the course of the study, or change in the product within 4
             months of baseline during the study

          -  Subject is a woman who is perimenopausal whos symptoms cause flushing that may affect
             the rosacea

          -  Systemic fungal infection

          -  History of active mycobacterial infection with any species within 3 years prior to
             screening, subjects with mycobacterium tuberculosis infection more than 3 years prior
             to screening are allowed if successful treatment was completed at least 3 years prior
             to randomization and is documented and available for verification

          -  Latent mycobacterium tuberculosis infection as indicated by a positive purified
             protein derivative (PPD) skin test. Subjects with a positive PPD skin test and
             documented completion of treatment for latent TB are eligible. Subjects with a
             positive PPD skin test and not treated or no documentation of completion of treatment
             are ineligible

          -  History of incompletely treated mycobacterium tuberculosis infection as indicated by:
             a)subject's medical records documenting incomplete treatment for mycobacterium
             tuberculosis b)subject's self reported history of incomplete treatment for
             mycobacterium tuberculosis

          -  History of recurrent bacterial infection (at least 3 major infections resulting in
             hospitalization and/or requiring intravenous antibiotic treatment within the past 2
             years)

          -  Clinically significant abnormality on the chest x-ray at screening, chest x-rays
             performed within 3 months prior to start of study drug are acceptable

          -  Any clinically significant abnormality on 12-lead electrocardiogram at screening

          -  History of congenital or acquired immunodeficiency (common variable immunodeficiency
             (CVID) Hepatitis B surface antigen positive or Hepatitis B core antibody positive at
             screening

          -  History of human immunodeficiency virus (HIV) infection

          -  Antibodies to hepatitis C at screening

          -  Malignancy or history of malignancy (except for treated/cured basal cell skin
             carcinoma) greater than 3 years prior to screening