Clinical trial NCT00539994: Retapamulin Ointment in Healthy Adults Nasally Colonized With Staphylococcus Aureus
Official title: Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics (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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Infections, Bacterial
Keywords: Altabax
SB-275833
retapamulin
nasal colonization
PK
tolerability
safety
efficacy
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2007-10-05
Enrollment: 57
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Primary outcomes:
measure: Plasma Retapumulin Pharmacokinetic Parameters by Treatment at Days 1 and 3 Evaluated by Plasma AUC After Dosing
timeFrame: Days 1 and 3
measure: Plasma Retapumulin Pharmacokinetic Parameters by Treatment at Day 5 Evaluated by Plasma AUC After Dosing
timeFrame: Day 5
measure: Plasma Retapumulin Pharmacokinetic Parameters by Treatment at Days 1 and 3 Evaluated by Plasma Cmax After Dosing
timeFrame: Days 1 and 3
measure: Plasma Retapumulin Pharmacokinetic Parameters by Treatment at Day 5 Evaluated by Plasma Cmax After Dosing
timeFrame: Day 5
measure: Percentage of Participants With Eradication of S. Aureus Nasal Carriage at Day 12 Who Were Categorized as Persistent Carriers of S. Aureus
timeFrame: Day 12
Secondary outcomes:
measure: Plasma Retapumulin Pharmacokinetic Parameters, Tmax, by Treatment at Days 1 and 3
timeFrame: Days 1 and 3
measure: Plasma Retapumulin Pharmacokinetic Parameters by Treatment at Day 5
timeFrame: Day 5
measure: Percentage of Participants With Eradication of S. Aureus Nasal Carriage at Days 7 and 33 Who Were Categorized as Persistent Carriers of S. Aureus
timeFrame: Days 7 and 33
measure: Percentage of Participants With Eradication of S. Aureus Nasal Carriage at Each Post Treatment Visit Stratified by Pharyngeal Carriage Status
timeFrame: Days 1, 7, 12, and 33
measure: Percentage of Participants With Nasal Recolonization With S. Aureus on Study Days 12 and 33 Who Were Persistant Carriers Who Tested Positive in the Pharyngeal Region on Days 12 and 33 But Negative in the Nasal Region on Day 7 or Days 7 and 12
timeFrame: Days 7, 12, and 33
measure: Prevalence of S. Aureus Nasal and Pharyngeal Carriage by Visit.
timeFrame: Screening Visits 1 (Day -42 to Day -14), 2 (Day -11 to Day -4), and 3 (Day -11 to Day -4) and Day 1
measure: Number of Participants With a Nasal Culture Negative for MRSA (Methicillin-resistant S. Aureus)
timeFrame: Days 7, 12, or 33.
Other outcomes:
measure: Percentage of Participants With Nasal Recolonization With S. Aureus on Study Days 12 and 33 Who Were Persistant Carriers Who Tested Positive in the Pharyngeal Region on Days 12 and 33 But Negative in the Nasal Region on Day 7 or Days 7 and 12
timeFrame: Days 7, 12, and 33.
Locations:
city: San Diego
country: United States
facility: GSK Investigational Site
state: California
city: Honolulu
country: United States
facility: GSK Investigational Site
state: Hawaii
city: Baltimore
country: United States
facility: GSK Investigational Site
state: Maryland
city: Tacoma
country: United States
facility: GSK Investigational Site
state: Washington
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Naderer OJ, Anderson M, Roberts K, Lou Y, Zhu J, Min S, Scangarella N, Shawar, R. Nasal Decolonization of Persistent Staphylococcus aureus Carriers with Twice Daily Retapamulin Treatment for 3 or 5 Days. Presentation Number L-1492. 48th ICAAC/46th IDSA Annual Meeting, Washington, DC, October 25-28, 2008.
citation: Naderer OJ, Anderson M, Roberts K, Scangarella N, Shawar R, Mundy LM. Case detection of Staphylococcus aureus colonization: screening of the anterior nares (AN) and throat (T). Presentation Number K-3353. 48th Interscience Conference on Antimicrobial Agents and Chemotheraty (ICAAC)/46th Infectious Diseases Society of America (IDSA) Annual Meeting, Washington, DC, October 25-28, 2008.
citation: Scangarella N, Naderer OJ, Anderson M, Roberts K, Sahm D, Shawar R. Antibacterial Activity of Retapamulin and Comparators Against Nasal and Pharyngeal Staphylococcus aureus Isolates Recovered from a Clinical Trial Investigating the Efficacy of Retapamulin in Nasal Decolonization. Presentation Number C1-3840. 48th ICAAC/46th IDSA Annual Meeting, Washington, DC, October 25-28, 2008.