Retapamulin Ointment in Healthy Adults Nasally Colonized With Staphylococcus Aureus

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.

ClinicalTrials.gov Identifier: NCT00539994

Recruitment Status : Completed

First Posted : October 5, 2007

Results First Posted : August 20, 2010

Last Update Posted : December 15, 2016

Sponsor:

Information provided by (Responsible Party):

GlaxoSmithKline

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Infections, Bacterial	Drug: retapamulin Drug: Retapamulin Drug: Placebo	Phase 2

Study Design

Layout table for study information

Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	57 participants
Allocation:	Randomized
Intervention Model:	Single Group Assignment
Masking:	Double (Participant, Investigator)
Primary Purpose:	Treatment
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 Start Date :	September 2007
Actual Primary Completion Date :	January 2008
Actual Study Completion Date :	January 2008

Resource links provided by the National Library of Medicine

Drug Information available for: Retapamulin

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Experimental: Treatment B 200mg BID retapamulin 5 days	Drug: Retapamulin 200mg BID retapamulin 5 days
Placebo Comparator: Treatment C 200mg BID placebo 5 days	Drug: Placebo 200mg BID placebo 5 days
Experimental: Treatment A 200mg BID retapamulin 3 days and placebo BID 2 days for a total of 5 days	Drug: retapamulin 200mg BID retapamulin 3 days

Outcome Measures

Primary Outcome Measures :

Plasma Retapumulin Pharmacokinetic Parameters by Treatment at Days 1 and 3 Evaluated by Plasma AUC After Dosing [ Time Frame: Days 1 and 3 ]
Area under the plasma concentration curve (AUC) is used to calculate drug clearance and bioavailability using plasma concentration and time curve.
Plasma Retapumulin Pharmacokinetic Parameters by Treatment at Day 5 Evaluated by Plasma AUC After Dosing [ Time Frame: Day 5 ]
Area under the plasma concentration curve (AUC) is used to calculate drug clearance and bioavailability using plasma concentration and time curve.
Plasma Retapumulin Pharmacokinetic Parameters by Treatment at Days 1 and 3 Evaluated by Plasma Cmax After Dosing [ Time Frame: Days 1 and 3 ]
Cmax is the peak serum concentration. Low value was not calculable, and High value was 2.74 ng/mL.
Plasma Retapumulin Pharmacokinetic Parameters by Treatment at Day 5 Evaluated by Plasma Cmax After Dosing [ Time Frame: Day 5 ]
Cmax is the peak serum concentration. Low value was not calculable, and high value was 2.74 ng/mL
Percentage of Participants With Eradication of S. Aureus Nasal Carriage at Day 12 Who Were Categorized as Persistent Carriers of S. Aureus [ Time Frame: Day 12 ]
Subjects who tested positive as persistent carriers of S. Aureus who on day 12 are negative and have been eradicated of S. Aureus.

Secondary Outcome Measures :

Plasma Retapumulin Pharmacokinetic Parameters, Tmax, by Treatment at Days 1 and 3 [ Time Frame: Days 1 and 3 ]
Tmax - The time after administration of a drug when the maximum plasma concentration is reached, when the rate of absorption equals the rate of elimination.
Plasma Retapumulin Pharmacokinetic Parameters by Treatment at Day 5 [ Time Frame: Day 5 ]
Tmax - The time after administration of a drug when the maximum plasma concentration is reached, when the rate of absorption equals the rate of elimination.
Percentage of Participants With Eradication of S. Aureus Nasal Carriage at Days 7 and 33 Who Were Categorized as Persistent Carriers of S. Aureus [ Time Frame: Days 7 and 33 ]
Subjects who tested positive as persistent carriers of S. Aureus who on Days 7 and 33 are negative and have eradicated of S. aureus.
Percentage of Participants With Eradication of S. Aureus Nasal Carriage at Each Post Treatment Visit Stratified by Pharyngeal Carriage Status [ Time Frame: Days 1, 7, 12, and 33 ]
Comparison of nasal S. aureus eradication in persistent carrier subjects on 7, 12, and 33 days after treatment stratified by S. aureus carriage in the pharyngeal area
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 [ Time Frame: Days 7, 12, and 33 ]
Percentage of subjects that were recolonized on Day 12 (D12) and Day 33 (D33) that were negative (neg.) for S. Aureus in the Pharyngeal region on days 12 or 33 and Negative in the Nasal Region on day 7 (D7) or days 7 and 12. Pharyngeal culture, PC; nasal culture, NC.
Prevalence of S. Aureus Nasal and Pharyngeal Carriage by Visit. [ Time Frame: Screening Visits 1 (Day -42 to Day -14), 2 (Day -11 to Day -4), and 3 (Day -11 to Day -4) and Day 1 ]
All participants were assessed for nasal and pharyngeal carriage at Screening Visits 1, 2, and 3. Participants were randomized into the study only if they had positive cultures at screening visit 1 and screening visit 2 and/or screening visit 3. Day 1 data were collected only for those participants who were randomized into the study.
Number of Participants With a Nasal Culture Negative for MRSA (Methicillin-resistant S. Aureus) [ Time Frame: Days 7, 12, or 33. ]
The number of participants who tested negative for MRSA on days 7, 12, and 33.

Other Outcome Measures:

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 [ Time Frame: Days 7, 12, and 33. ]
All subjects were positive (pos.) for S. Aureus in the Pharyngeal region on days 12 or 33 (D12 and D33) and Negative (neg.) in the Nasal Region on day 7 (D7) or days 7 and 12. Pharyngeal culture, PC; nasal culture, NC.

Eligibility Criteria

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information

Ages Eligible for Study:	18 Years to 65 Years (Adult, Older Adult)
Sexes Eligible for Study:	All
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00539994

Locations

Layout table for location information

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

Layout table for investigator information

Study Director:	GSK Clinical Trials	GlaxoSmithKline

More Information

Additional Information:

Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research. This link exits the ClinicalTrials.gov site