Clinical Endpoint Study of Ivermectin 1% Cream
Condition: Moderate to Severe Papulopustular Rosacea
MeSH terms: Rosacea
Intervention: Ivermectin Cream, 1%; Placebo/Vehicle cream
Intervention MeSH terms: Ivermectin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 630.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      A randomized, double-blind, placebo-controlled, parallel-design, multiple-site clinical study
      to evaluate the therapeutic equivalence and safety of ivermectin cream 1% (Actavis
      Laboratories UT, Inc.) to SoolantraTM (ivermectin) cream 1% (Galderma) in the treatment of
      moderate to severe papulopustular rosacea.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Signed Informed Consent that meets all criteria of current FDA regulations.

          2. Healthy male or non-pregnant, non-lactating female greater than or equal to 8 years of
             age with a clinical diagnosis of moderate to severe papulopustular rosacea, defined as
             the presence of:

             A total of 8 to 50 combined papules/pustules on the face, AND At least moderate
             erythema, AND Telangiectasia

          3. Patient has a baseline Investigator's Global Evaluation (IGE) score of 3 (moderate) or
             4 (severe) for rosacea severity (See Appendix A).

          4. Females of child bearing potential must not be pregnant or lactating at Screening (as
             confirmed by a negative urine pregnancy test with a sensitivity of less than 25 mlU/mL
             or equivalent units of human chorionic gonadotropin). Women of childbearing potential
             must agree to the use of a reliable method of contraception (e.g., total abstinence,
             IUD, a double-barrier method [such as condom plus diaphragm with spermicide], oral,
             transdermal, injected or implanted non- or hormonal contraceptive), throughout the
             study. If the female is using a hormonal contraceptive, the same product must be taken
             for 3 months prior to Visit 1 and must agree not to replace with some other hormonal
             contraceptives during the study. A sterile sexual partner is not considered an
             adequate form of birth control.

             All females will be considered to be of childbearing potential unless they: Are
             post-menopausal, defined as women who have been amenorrheic for at least 12
             consecutive months, without other known or suspected primary cause.

             Have been sterilized surgically or who are otherwise proven sterile (i.e., total
             hysterectomy, or bilateral oophorectomy) with surgery at least 4 weeks before
             Screening. Tubal ligation will not be considered a surgically sterile method.

             Female patients of childbearing potential are defined as Women without prior
             hysterectomy of at least 4 weeks, or who have had any evidence of menses in the past
             12 months.

             Females who have been amenorrhea for more than or equal to 12 months, but the
             amenorrhea is possibly due to other causes, including prior chemotherapy,
             anti-estrogens, or ovarian suppression.

          5. Free from any systemic or dermatologic disorder that, in the opinion of the
             Investigator, will interfere with the study results or increase the risk of adverse
             events.

          6. Willing to minimize external factors that might trigger rosacea flare-ups (e.g.,
             extreme temperatures, aggressive astringents, known offending foods such as spicy
             foods and thermally hot foods and drinks, prolonged sun exposure, strong winds,
             alcoholic beverages, and emotional stress) within 24 hours before the Screening visit.

          7. Of any skin type or race, provided the skin pigmentation allows accurate evaluation of
             papulopustular rosacea.

          8. Willingness and capability to cooperate to the extent and degree required by the
             protocol.

        Exclusion Criteria:

          1. Females who are pregnant, lactating or planning to become pregnant during the study
             period.

          2. Patient has mild facial rosacea (less than 8 inflammatory lesions on the face) or very
             severe rosacea (more than 50 inflammatory lesions).

          3. Patient has mild erythema.

          4. Patient has a baseline IGE score of 0, 1 or 2.

          5. Patient has a skin condition on the face that would interfere with the diagnosis or
             assessment of rosacea (e.g., dermatitis, psoriasis, squamous cell carcinoma, eczema,
             acneform eruptions caused by medications, steroid acne, steroid folliculitis,
             bacterial folliculitis).

          6. Patients with excessive facial hair, such as beards, sideburns, moustaches, etc., that
             would interfere with diagnosis or assessment of rosacea.

          7. Patients with tattoos or excessive facial scarring that, in the Investigator's
             opinion, may interfere with the evaluation of the patient's rosacea.

          8. Patients with active facial sunburn, peeling from sunburn, or patients that will be
             exposed to excessive sunlight during the study.

          9. Patient has significant history or current evidence of chronic infectious disease,
             system disorder, organ disorder or other medical condition that in the Investigator's
             opinion would place the study patient at undue risk by participation.

         10. Any patient (male or female) who has started, or changed hormonal therapy within 3
             months of the baseline visit (this includes hormonal contraceptives). Patients who
             have been on stable hormone therapy for at least 3 months and whose therapy is
             considered unlikely to be changed for the duration of the study will be eligible.

         11. History of hypersensitivity or allergy to study drug, or other ingredients of the
             formulation.

         12. Use within 6 months prior to baseline of oral retinoids (e.g., Accutane) or
             therapeutic vitamin A supplements of greater than 10,000 units/day (multivitamins are
             allowed).

         13. Use for less than 3 months prior to baseline of estrogen- and/or progestin-containing
             oral, injectable, implant, or transdermal contraceptives; use of such therapy must
             remain constant throughout the study.

         14. Use within 1 month prior to baseline of 1) topical retinoids to the face, 2) systemic
             (e.g., oral or injectable) antibiotics known to have an impact on the severity of
             facial rosacea (e.g., containing tetracycline and its derivatives, erythromycin and
             its derivatives, sulfamethoxazole, or trimethoprim), 3) systemic steroids, 4)
             photodynamic therapy (including laser and other light therapies), or 6) cosmetic
             procedures (e.g., superficial chemical peels, exfoliation or microdermabrasion of the
             face).

         15. Use within 2 weeks prior to baseline of 1) topical corticosteroids, 2) topical
             antibiotics, 3) topical anti-inflammatory agents or 4) topical medications for rosacea
             (e.g., metronidazole, azelaic acid, sodium sulfacetamide, ivermectin) 5)
             immunosuppressive drugs, 6) anticoagulant therapy.

         16. Use of any other topical products applied to the target site.

         17. Use of systemic corticosteroids. The use of inhaled corticosteroids up to less than
             1mg per day is acceptable.

         18. Use of antipruritics, including antihistamines, within 24 hours of study visits.

         19. Patients who use make-up must have used the same brands/types for a minimum period of
             14 days before study entry and must agree to not change brand or frequency of use
             throughout the study.

         20. Presence of carcinoid, pheochromocytoma, or other causes of systemic flushing.

         21. Presence of acne conglobata, acne fulminans, secondary acne or severe acne requiring
             systemic treatment.

         22. Ocular rosacea (e.g., conjunctivitis, blepharitis, or keratitis) of sufficient
             severity to require topical or systemic antibiotics.

         23. Receipt of any drug as part of a research study within 30 days before dosing.

         24. Employees of the research center or Investigator.

         25. Patients who are illiterate