Retapamulin Ointment in Healthy Adults Nasally Colonized With Staphylococcus Aureus
Condition: Infections, Bacterial
MeSH terms: Bacterial Infections
Intervention: retapamulin; Retapamulin; Placebo
Intervention description: 200mg BID retapamulin 3 days; 200mg BID retapamulin 5 days; 200mg BID placebo 5 days
Intervention MeSH terms: Retapamulin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: Double (Participant, Investigator)
Enrollment: 57.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Altabax; SB-275833; retapamulin; nasal colonization; PK; tolerability; safety; efficacy

Summary:

      This is a Phase I/IIa randomized, double-blind, placebo-controlled study to evaluate the
      safety, tolerability, PK, and efficacy of Retapamulin ointment, 1% applied twice daily for 3
      or 5 days to the anterior nares of healthy adult subjects who are nasally colonized with S.
      aureus. Approximately 57 healthy subjects who are nasal carriers of S. aureus will be
      enrolled and stratified in a 2:1 ratio so that at least 38 persistent carriers and 19
      intermittent carriers complete the study. Each eligible subject will participate in three
      screening visits, a treatment period, and two follow-up visits. Each subject's participation
      in the study will be approximately 6 to 10 weeks from screening to the last follow-up visit.
      Subjects will participate in up to three screening visits to determine S. aureus culture
      positivity and colonization status.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male and female subjects between the ages of 18 and 65, inclusive. A female is
             eligible to enter and participate in this study if she is non-pregnant, nonlactating
             and if she is of:

               -  non-childbearing potential (i.e., physiologically incapable of becoming
                  pregnant), including pre-menopausal females with documented (medical report
                  verification) hysterectomy or double oophorectomy or documented tubal ligation or
                  post-menopausal females defined as being amenorrheic for greater than one year
                  and having follicle stimulating hormone (FSH) levels consistent with menopause.

               -  child-bearing potential has a negative pregnancy test at screening. In addition,
                  she must be willing to abstain from sexual intercourse or must use a nonhormone
                  contraception such as an IUD or diaphragm with spermicide, in addition to having
                  their male partner use condom/spermicide. This criterion must be followed from at
                  least the commencement of her last normal period prior to the first dose of study
                  medication or from screening (whichever is earlier) until completion of all
                  follow-up procedures (33 days after the last dose of study medication).

          -  Body weight ≥ 50 kg for men and ≥ 45 kg for women and a body mass index (BMI) between
             18.5 - 33 kg/m2.

          -  The subject is able to understand and comply with requirements, instructions and
             restrictions listed in the consent form.

          -  Signed and dated written informed consent prior to admission to the study.

        Exclusion Criteria:

          -  Negative nasal culture for S. aureus on the first screen visit.

          -  Negative nasal cultures for S. aureus on second and third screen visits.

          -  Concurrent treatment with antimicrobials for an infection.

          -  MRSA decolonization attempt in the previous 6 months (prior treatment for a MRSA
             infection is not an exclusion criterion).

          -  Inability to take medications nasally.

          -  Nasal surgery in the previous 3 months.

          -  Evidence of active rhinitis, sinusitis, or upper respiratory infection.

          -  Within the judgment of the Principal Investigator and the Sponsor Medical Monitor, any
             clinically significant hematologic, endocrine, cardiovascular, hepatic, renal,
             gastrointestinal, and/or pulmonary disorder; any predisposing condition that might
             interfere with the absorption, distribution, metabolism, and/or excretion of drugs; or
             any clinically relevant abnormality identified on physical examination, 12-lead ECG,
             or clinical laboratories at screening. A single repeat for clinical laboratories or
             12- lead ECG will be allowed to determine eligibility.

          -  The subject's systolic BP is outside the range of 90-150mmHg, or diastolic BP is
             outside the range of 45-95mmHg or HR is outside the range of 50-100 bpm for female
             subjects or 40-100 bpm for male subjects.

          -  Subjects who have a history of allergy to the study drug or drugs of this class, or a
             history of drug or other allergy that, in the opinion of the investigator,
             contraindicates participation in the trial. In addition, if heparin is used during PK
             sampling, subjects with a history of sensitivity to heparin or heparin-induced
             thrombocytopenia should not be enrolled.

          -  The use of prescription or non-prescription drugs, including vitamins, herbal and
             dietary supplements (including St. John's Wort) within 7 days (or 14 days if the drug
             is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the
             first dose of study medication, unless in the opinion of Investigator and Sponsor the
             medication will not interfere with the study procedures or compromise subject safety.
             Use of nasal medications is strictly prohibited from 7 days prior to the first
             screening visit and then 7 days prior to the 2nd screening visit through the final
             follow-up visit.

          -  Treatment with an investigational drug within 30 days or five half-lives (whichever is
             longer) preceding the first dose of study medication.

          -  The subject has a history of alcohol or substance abuse or dependence within 12 months
             of the study: History of regular alcohol consumption averaging > 7 drinks/wk for women
             or > 14 drinks/wk for men. 1 drink is equivalent to 12g alcohol = 5 oz (150ml) of wine
             or 12oz (360ml) of beer or 1.5 oz (45ml) of 80 proof distilled spirits within six
             months of screening.

          -  Positive for Human Immunodeficiency Virus (HIV) antibody, hepatitis B virus surface
             antigen or hepatitis C virus antibody at screening.

          -  Donation of blood in excess of 500 mL within 56 days prior to dosing. Note: This does
             not include plasma donation.

          -  The subject has a positive urine drug or alcohol screen.

          -  The subject has a history of illicit drug abuse or is unwilling to refrain from the
             use of illicit drugs and adhere to other protocol-stated restrictions while
             participating in the study.