Retapamulin Ointment in Healthy Adults Nasally Colonized With Staphylococcus Aureus

NCT00539994 | Completed Phase 2 Results

• 1 other identifier: ALB110247
• Study Type: interventional
• Target: 57
• Locations: 1 country
• Sites: 4

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.

Conditions

Infections, Bacterial

Keywords

Altabax; SB-275833; retapamulin; nasal colonization; PK; tolerability; safety; efficacy

Outcome Measures

Primary Outcomes (5)

• Plasma Retapumulin Pharmacokinetic Parameters by Treatment at Days 1 and 3 Evaluated by Plasma AUC After Dosing

  Area under the plasma concentration curve (AUC) is used to calculate drug clearance and bioavailability using plasma concentration and time curve.

  Days 1 and 3

• Plasma Retapumulin Pharmacokinetic Parameters by Treatment at Day 5 Evaluated by Plasma AUC After Dosing

  Area under the plasma concentration curve (AUC) is used to calculate drug clearance and bioavailability using plasma concentration and time curve.

  Day 5

• Plasma Retapumulin Pharmacokinetic Parameters by Treatment at Days 1 and 3 Evaluated by Plasma Cmax After Dosing

  Cmax is the peak serum concentration. Low value was not calculable, and High value was 2.74 ng/mL.

  Days 1 and 3

• Plasma Retapumulin Pharmacokinetic Parameters by Treatment at Day 5 Evaluated by Plasma Cmax After Dosing

  Cmax is the peak serum concentration. Low value was not calculable, and high value was 2.74 ng/mL

  Day 5

• Percentage of Participants With Eradication of S. Aureus Nasal Carriage at Day 12 Who Were Categorized as Persistent Carriers of S. Aureus

  Subjects who tested positive as persistent carriers of S. Aureus who on day 12 are negative and have been eradicated of S. Aureus.

  Day 12

Secondary Outcomes (7)

• Plasma Retapumulin Pharmacokinetic Parameters, Tmax, by Treatment at Days 1 and 3

  Days 1 and 3

• Plasma Retapumulin Pharmacokinetic Parameters by Treatment at Day 5

  Day 5

• Percentage of Participants With Eradication of S. Aureus Nasal Carriage at Days 7 and 33 Who Were Categorized as Persistent Carriers of S. Aureus

  Days 7 and 33

• Percentage of Participants With Eradication of S. Aureus Nasal Carriage at Each Post Treatment Visit Stratified by Pharyngeal Carriage Status

  Days 1, 7, 12, and 33

• 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

  Days 7, 12, and 33

Other Outcomes (1)

• 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

  Days 7, 12, and 33.

Study Arms (3)

Treatment B

EXPERIMENTAL

200mg BID retapamulin 5 days

Drug: Retapamulin

Treatment C

PLACEBO COMPARATOR

200mg BID placebo 5 days

Drug: Placebo

Treatment A

EXPERIMENTAL

200mg BID retapamulin 3 days and placebo BID 2 days for a total of 5 days

Drug: retapamulin

Interventions

Retapamulin DRUG

200mg BID retapamulin 3 days

Treatment A

Placebo DRUG

200mg BID placebo 5 days

Treatment C

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (4)

GSK Investigational Site

San Diego, California, 92123, United States

Location

GSK Investigational Site

Honolulu, Hawaii, 96813, United States

Location

GSK Investigational Site

Baltimore, Maryland, 21225, United States

Location

GSK Investigational Site

Tacoma, Washington, 98418, United States

Location

Related Publications (3)

• 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.

  BACKGROUND

• 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.

  BACKGROUND

• 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.

  BACKGROUND

Related Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

MeSH Terms

Conditions

Bacterial Infections

Interventions

retapamulin

Condition Hierarchy (Ancestors)

Bacterial Infections and Mycoses; Infections

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 4, 2007
• First Posted: October 5, 2007
• Study Start: September 1, 2007
• Primary Completion: January 1, 2008
• Study Completion: January 1, 2008
• Last Updated: December 15, 2016
• Results First Posted: August 20, 2010

Record last verified: 2016-11

Data Sharing

• IPD Sharing: Will share

Locations

US (4)