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Retapamulin Ointment in Healthy Adults Nasally Colonized With Staphylococcus Aureus
This study has been completed.
Sponsored by: GlaxoSmithKline
Information provided by: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00539994
  Purpose

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.


Condition Intervention Phase
Nasal Colonization With S. Aureus
Drug: retapamulin
Phase II

Drug Information available for: Retapamulin
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Randomized, Double-Blind, Single Group Assignment, Safety/Efficacy Study
Official Title: 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 Nasally Colonized With Staphylococcus Aureus

Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Retapamulin safety and tolerability parameters. Plasma AUC and Cmax after the first dose [ Time Frame: on Study Days 1, 3, and Day 5. ]
  • Percent of subjects in the persistent carrier stratum with a nasal culture negative for S. aureus. [ Time Frame: on Study Day 7 ]

Secondary Outcome Measures:
  • Plasma tmax, AUC and t1/2, % with a nasal culture negative, % with a positive nasal or pharyngeal culture, % who have nasal recolonization after a negative nasal culture stratified by pharyngeal culture, prevalence from screened subjects of S. aureus
  • Plasma tmax, AUC(0-∞) and t1/2 of retapamulin after the first dose as data permit. [ Time Frame: on Study Days 1, 3, and 5, ]
  • Percent of subjects with a nasal culture negative for S. aureus [ Time Frame: on Study Days 7 or 33. ]
  • Percent of subjects with a nasal culture positive for S. aureus in subjects with a pharyngeal culture positive or negative for S. aureus. [ Time Frame: on Study Days 7, 12, or 33 ]
  • Percent of subjects who have nasal recolonization with S. aureus on Study Day 12 or Day 33 after a negative nasal culture for S. aureus on Day 7, stratified by pharyngeal culture on Days 12 or 33, respectively. [ Time Frame: on Study Day 12 or Day 33 ]
  • Prevalence of S. aureus isolates obtained from nasal and pharyngeal swabs of the screened subjects.
  • Percent of subjects with a nasal culture negative for MRSA [ Time Frame: on Study Days 7, 12, or 33. ]

Enrollment: 57
Study Start Date: September 2007
Estimated Study Completion Date: January 2008
  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00539994

Locations
United States, California
GSK Investigational Site
San Diego, California, United States, 92123
United States, Hawaii
GSK Investigational Site
Honolulu, Hawaii, United States, 96813
United States, Maryland
GSK Investigational Site
Baltimore, Maryland, United States, 21225
United States, Washington
GSK Investigational Site
Tacoma, Washington, United States, 98418
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials, PharmD GlaxoSmithKline
  More Information

Responsible Party: GSK ( Study Director )
Study ID Numbers: ALB110247
Study First Received: October 4, 2007
Last Updated: October 15, 2008
ClinicalTrials.gov Identifier: NCT00539994  
Health Authority: United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:
retapamulin
SB-275833
Altabax
safety
tolerability
PK
efficacy
nasal colonization

Study placed in the following topic categories:
Healthy

ClinicalTrials.gov processed this record on January 16, 2009