Infections, Bacterial
Conditions
Keywords
Altabax, SB-275833, retapamulin, nasal colonization, PK, tolerability, safety, efficacy
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.
Interventions
DRUGretapamulin
200mg BID retapamulin 3 days
DRUGRetapamulin
200mg BID retapamulin 5 days
DRUGPlacebo
200mg BID placebo 5 days
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Eradication of S. Aureus Nasal Carriage at Day 12 Who Were Categorized as Persistent Carriers of S. Aureus | 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. |
| Plasma Retapumulin Pharmacokinetic Parameters by Treatment at Days 1 and 3 Evaluated by Plasma AUC After Dosing | 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 | 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 | 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 | Day 5 | Cmax is the peak serum concentration. Low value was not calculable, and high value was 2.74 ng/mL |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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 |
| Prevalence of S. Aureus Nasal and Pharyngeal Carriage by Visit. | 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. |
| 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 | 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. |
| Number of Participants With a Nasal Culture Negative for MRSA (Methicillin-resistant S. Aureus) | Days 7, 12, or 33. | The number of participants who tested negative for MRSA on days 7, 12, and 33. |
| Plasma Retapumulin Pharmacokinetic Parameters, Tmax, by Treatment at Days 1 and 3 | 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 | 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 | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| 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. | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Retapamulin 3 Days Retapamulin ointment, 1% 200 mg BID 3 days and 200 mg Placebo BID for 2 days | 23 |
| Retapamulin 5 Days Retapamulin ointment, 1% 200 mg BID 5 days | 19 |
| Placebo Placebo 200 mg BID for 5 days | 15 |
| Total | 57 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 2 | 1 | 0 |
| Overall Study | Physician Decision | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 1 |
Baseline characteristics
| Characteristic | Retapamulin 3 Days | Retapamulin 5 Days | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 31.8 Years STANDARD_DEVIATION 10.8 | 35.8 Years STANDARD_DEVIATION 11.16 | 33.7 Years STANDARD_DEVIATION 12.67 | 33.6 Years STANDARD_DEVIATION 11.36 |
| Efficacy population by carrier type (persistent vs intermittent) Excluded from analysis | 5 participants | 1 participants | 2 participants | 8 participants |
| Efficacy population by carrier type (persistent vs intermittent) Intermittent, Intent-to-Treat | 1 participants | 2 participants | 0 participants | 3 participants |
| Efficacy population by carrier type (persistent vs intermittent) Persistent, Intent-to-Treat | 17 participants | 16 participants | 13 participants | 46 participants |
| Gender Female | 6 Participants | 6 Participants | 2 Participants | 14 Participants |
| Gender Male | 17 Participants | 13 Participants | 13 Participants | 43 Participants |
| Race/Ethnicity, Customized African American/African Heritage | 4 Participants | 7 Participants | 3 Participants | 14 Participants |
| Race/Ethnicity, Customized Asian - East Asian Heritage | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian - Japanese Heritage | 0 Participants | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Asian - South East Asian Heritage | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 1 participants | 1 participants | 2 participants | 4 participants |
| Race/Ethnicity, Customized Mixed Race | 1 Participants | 2 Participants | 2 Participants | 5 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 22 participants | 18 participants | 13 participants | 53 participants |
| Race/Ethnicity, Customized White | 18 Participants | 7 Participants | 9 Participants | 34 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 6 / 23 | 10 / 19 | 5 / 15 |
| serious Total, serious adverse events | 0 / 23 | 1 / 19 | 0 / 15 |
Outcome results
Primary
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.
Time frame: Day 12
Population: Per Protocol Population: Persistent Carriers of the Intent-to-Treat (ITT) Population who Tested Positive on Screening Visit 1, 2 and 3.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Retapamulin 3 Days | Percentage of Participants With Eradication of S. Aureus Nasal Carriage at Day 12 Who Were Categorized as Persistent Carriers of S. Aureus | 94 Percentage of participants |
| Retapamulin 5 Days | Percentage of Participants With Eradication of S. Aureus Nasal Carriage at Day 12 Who Were Categorized as Persistent Carriers of S. Aureus | 92 Percentage of participants |
| Placebo | Percentage of Participants With Eradication of S. Aureus Nasal Carriage at Day 12 Who Were Categorized as Persistent Carriers of S. Aureus | 15 Percentage of participants |
p-value: <0.001Fisher Exact
p-value: <0.001Fisher Exact
Primary
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.
Time frame: Day 5
Population: Pharmacokinetic Concentration Population - included all subjects who underwent plasma PK sampling
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Retapamulin 5 Days | Plasma Retapumulin Pharmacokinetic Parameters by Treatment at Day 5 Evaluated by Plasma AUC After Dosing | 1.8883 ng.h/mL | Standard Deviation 3.05391 |
Primary
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
Time frame: Day 5
Population: Pharmacokinetic Concentration Population - included all subjects who underwent plasma PK sampling
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Retapamulin 5 Days | Plasma Retapumulin Pharmacokinetic Parameters by Treatment at Day 5 Evaluated by Plasma Cmax After Dosing | 0.5547 ng/mL | Standard Deviation 0.31469 |
Primary
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.
Time frame: Days 1 and 3
Population: Pharmacokinetic (PK) Concentration Population - included all subjects who underwent plasma PK sampling
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Retapamulin 3 Days | Plasma Retapumulin Pharmacokinetic Parameters by Treatment at Days 1 and 3 Evaluated by Plasma AUC After Dosing | Day 1, n=5 and 2 | 0.8663 ng.h /mL | Standard Deviation 1.77269 |
| Retapamulin 3 Days | Plasma Retapumulin Pharmacokinetic Parameters by Treatment at Days 1 and 3 Evaluated by Plasma AUC After Dosing | Day 3, n=14 and 10 | 4.2802 ng.h /mL | Standard Deviation 5.37822 |
| Retapamulin 5 Days | Plasma Retapumulin Pharmacokinetic Parameters by Treatment at Days 1 and 3 Evaluated by Plasma AUC After Dosing | Day 1, n=5 and 2 | 0.3816 ng.h /mL | Standard Deviation 0.89226 |
| Retapamulin 5 Days | Plasma Retapumulin Pharmacokinetic Parameters by Treatment at Days 1 and 3 Evaluated by Plasma AUC After Dosing | Day 3, n=14 and 10 | 2.0881 ng.h /mL | Standard Deviation 3.47126 |
Primary
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.
Time frame: Days 1 and 3
Population: Pharmacokinetic Concentration Population - included all subjects who underwent plasma PK sampling
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Retapamulin 3 Days | Plasma Retapumulin Pharmacokinetic Parameters by Treatment at Days 1 and 3 Evaluated by Plasma Cmax After Dosing | Day 1, n=10 and 3 | 0.4703 ng/mL | Standard Deviation 0.34262 |
| Retapamulin 3 Days | Plasma Retapumulin Pharmacokinetic Parameters by Treatment at Days 1 and 3 Evaluated by Plasma Cmax After Dosing | Day 3, n=16 and 10 | 0.7893 ng/mL | Standard Deviation 0.56984 |
| Retapamulin 5 Days | Plasma Retapumulin Pharmacokinetic Parameters by Treatment at Days 1 and 3 Evaluated by Plasma Cmax After Dosing | Day 1, n=10 and 3 | 0.3538 ng/mL | Standard Deviation 0.27237 |
| Retapamulin 5 Days | Plasma Retapumulin Pharmacokinetic Parameters by Treatment at Days 1 and 3 Evaluated by Plasma Cmax After Dosing | Day 3, n=16 and 10 | 0.6185 ng/mL | Standard Deviation 0.46093 |
Secondary
Number of Participants With a Nasal Culture Negative for MRSA (Methicillin-resistant S. Aureus)
The number of participants who tested negative for MRSA on days 7, 12, and 33.
Time frame: Days 7, 12, or 33.
Population: Screening Eligibility Population: only participants who provided nasal cultures at Days 7, 12, and 33 were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Retapamulin 3 Days | Number of Participants With a Nasal Culture Negative for MRSA (Methicillin-resistant S. Aureus) | Day 33, n=17 | 17 participants |
| Retapamulin 3 Days | Number of Participants With a Nasal Culture Negative for MRSA (Methicillin-resistant S. Aureus) | Day 7, n=12 | 12 participants |
| Retapamulin 3 Days | Number of Participants With a Nasal Culture Negative for MRSA (Methicillin-resistant S. Aureus) | Day 12, n=14 | 13 participants |
Secondary
Percentage of Participants With Eradication of S. Aureus Nasal Carriage at Days 7 and 33 Who Were Categorized as Persistent Carriers of S. Aureus
Subjects who tested positive as persistent carriers of S. Aureus who on Days 7 and 33 are negative and have eradicated of S. aureus.
Time frame: Days 7 and 33
Population: Per Protocol Population: Persistent Carriers of the Intent-to-Treat (ITT) Population who Tested Positive on Screening Visits 1, 2 and 3.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Retapamulin 3 Days | Percentage of Participants With Eradication of S. Aureus Nasal Carriage at Days 7 and 33 Who Were Categorized as Persistent Carriers of S. Aureus | Day 7 | 94 Percentage of participants |
| Retapamulin 3 Days | Percentage of Participants With Eradication of S. Aureus Nasal Carriage at Days 7 and 33 Who Were Categorized as Persistent Carriers of S. Aureus | Day 33 | 75 Percentage of participants |
| Retapamulin 5 Days | Percentage of Participants With Eradication of S. Aureus Nasal Carriage at Days 7 and 33 Who Were Categorized as Persistent Carriers of S. Aureus | Day 7 | 100 Percentage of participants |
| Retapamulin 5 Days | Percentage of Participants With Eradication of S. Aureus Nasal Carriage at Days 7 and 33 Who Were Categorized as Persistent Carriers of S. Aureus | Day 33 | 86 Percentage of participants |
| Placebo | Percentage of Participants With Eradication of S. Aureus Nasal Carriage at Days 7 and 33 Who Were Categorized as Persistent Carriers of S. Aureus | Day 7 | 2 Percentage of participants |
| Placebo | Percentage of Participants With Eradication of S. Aureus Nasal Carriage at Days 7 and 33 Who Were Categorized as Persistent Carriers of S. Aureus | Day 33 | 4 Percentage of participants |
Secondary
Percentage of Participants With Eradication of S. Aureus Nasal Carriage at Each Post Treatment Visit Stratified by Pharyngeal Carriage Status
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
Time frame: Days 1, 7, 12, and 33
Population: Per Protocol Population: Persistent Carriers of the Intent-to-Treat (ITT) Population who Tested Positive on Screening Visit 1, 2, 3, and who were Persistent Nasal carriers who were both positive and negative carriers of S. aureus in the Pharyngeal region.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Retapamulin 3 Days | Percentage of Participants With Eradication of S. Aureus Nasal Carriage at Each Post Treatment Visit Stratified by Pharyngeal Carriage Status | Culture positive Day 1, Nasal eradication Day 7 | 90 Percentage of participants |
| Retapamulin 3 Days | Percentage of Participants With Eradication of S. Aureus Nasal Carriage at Each Post Treatment Visit Stratified by Pharyngeal Carriage Status | Culture negative Day 1, Nasal eradication Day 7 | 100 Percentage of participants |
| Retapamulin 3 Days | Percentage of Participants With Eradication of S. Aureus Nasal Carriage at Each Post Treatment Visit Stratified by Pharyngeal Carriage Status | Culture positive Day 1, Nasal eradication Day 12 | 90 Percentage of participants |
| Retapamulin 3 Days | Percentage of Participants With Eradication of S. Aureus Nasal Carriage at Each Post Treatment Visit Stratified by Pharyngeal Carriage Status | Culture negative Day 1, Nasal eradication Day 12 | 100 Percentage of participants |
| Retapamulin 3 Days | Percentage of Participants With Eradication of S. Aureus Nasal Carriage at Each Post Treatment Visit Stratified by Pharyngeal Carriage Status | Culture positive Day 1, Nasal eradication Day 33 | 80 Percentage of participants |
| Retapamulin 3 Days | Percentage of Participants With Eradication of S. Aureus Nasal Carriage at Each Post Treatment Visit Stratified by Pharyngeal Carriage Status | Culture negative Day 1, Nasal eradication Day 33 | 67 Percentage of participants |
| Retapamulin 5 Days | Percentage of Participants With Eradication of S. Aureus Nasal Carriage at Each Post Treatment Visit Stratified by Pharyngeal Carriage Status | Culture negative Day 1, Nasal eradication Day 33 | 83 Percentage of participants |
| Retapamulin 5 Days | Percentage of Participants With Eradication of S. Aureus Nasal Carriage at Each Post Treatment Visit Stratified by Pharyngeal Carriage Status | Culture positive Day 1, Nasal eradication Day 7 | 100 Percentage of participants |
| Retapamulin 5 Days | Percentage of Participants With Eradication of S. Aureus Nasal Carriage at Each Post Treatment Visit Stratified by Pharyngeal Carriage Status | Culture negative Day 1, Nasal eradication Day 12 | 100 Percentage of participants |
| Retapamulin 5 Days | Percentage of Participants With Eradication of S. Aureus Nasal Carriage at Each Post Treatment Visit Stratified by Pharyngeal Carriage Status | Culture positive Day 1, Nasal eradication Day 33 | 88 Percentage of participants |
| Retapamulin 5 Days | Percentage of Participants With Eradication of S. Aureus Nasal Carriage at Each Post Treatment Visit Stratified by Pharyngeal Carriage Status | Culture negative Day 1, Nasal eradication Day 7 | 100 Percentage of participants |
| Retapamulin 5 Days | Percentage of Participants With Eradication of S. Aureus Nasal Carriage at Each Post Treatment Visit Stratified by Pharyngeal Carriage Status | Culture positive Day 1, Nasal eradication Day 12 | 86 Percentage of participants |
| Placebo | Percentage of Participants With Eradication of S. Aureus Nasal Carriage at Each Post Treatment Visit Stratified by Pharyngeal Carriage Status | Culture negative Day 1, Nasal eradication Day 7 | 33 Percentage of participants |
| Placebo | Percentage of Participants With Eradication of S. Aureus Nasal Carriage at Each Post Treatment Visit Stratified by Pharyngeal Carriage Status | Culture positive Day 1, Nasal eradication Day 12 | 10 Percentage of participants |
| Placebo | Percentage of Participants With Eradication of S. Aureus Nasal Carriage at Each Post Treatment Visit Stratified by Pharyngeal Carriage Status | Culture negative Day 1, Nasal eradication Day 33 | 33 Percentage of participants |
| Placebo | Percentage of Participants With Eradication of S. Aureus Nasal Carriage at Each Post Treatment Visit Stratified by Pharyngeal Carriage Status | Culture negative Day 1, Nasal eradication Day 12 | 33 Percentage of participants |
| Placebo | Percentage of Participants With Eradication of S. Aureus Nasal Carriage at Each Post Treatment Visit Stratified by Pharyngeal Carriage Status | Culture positive Day 1, Nasal eradication Day 7 | 10 Percentage of participants |
| Placebo | Percentage of Participants With Eradication of S. Aureus Nasal Carriage at Each Post Treatment Visit Stratified by Pharyngeal Carriage Status | Culture positive Day 1, Nasal eradication Day 33 | 30 Percentage of participants |
Secondary
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
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.
Time frame: Days 7, 12, and 33
Population: Per Protocol Population: Persistent Carriers of the Intent-to-Treat (ITT) Population who Tested Positive on Screening Visit 1, 2, 3 and those who were NEGATIVE for Pharynegeal Carriage on Day 12 and Day 33 then recolonized.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Retapamulin 3 Days | 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 | PC neg. D12, NC neg. D7, Recolonized D12 | 11 Percentage of participants |
| Retapamulin 3 Days | 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 | PC neg. D12, NC neg. D7 and D12, Recolonized D33 | 13 Percentage of participants |
| Retapamulin 3 Days | 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 | PC neg. D33, NC neg. D7 and D12, Recolonized D33 | 11 Percentage of participants |
| Retapamulin 3 Days | 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 | PC neg. D33, NC neg. D7, Recolonized D12 | 0 Percentage of participants |
| Retapamulin 5 Days | 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 | PC neg. D12, NC neg. D7, Recolonized D12 | 0 Percentage of participants |
| Retapamulin 5 Days | 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 | PC neg. D33, NC neg. D7 and D12, Recolonized D33 | 13 Percentage of participants |
| Retapamulin 5 Days | 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 | PC neg. D12, NC neg. D7 and D12, Recolonized D33 | 20 Percentage of participants |
| Retapamulin 5 Days | 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 | PC neg. D33, NC neg. D7, Recolonized D12 | 0 Percentage of participants |
| Placebo | 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 | PC neg. D12, NC neg. D7, Recolonized D12 | 0 Percentage of participants |
| Placebo | 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 | PC neg. D33, NC neg. D7 and D12, Recolonized D33 | 0 Percentage of participants |
| Placebo | 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 | PC neg. D33, NC neg. D7, Recolonized D12 | 100 Percentage of participants |
| Placebo | 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 | PC neg. D12, NC neg. D7 and D12, Recolonized D33 | 0 Percentage of participants |
| Total | 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 | PC neg. D33, NC neg. D7 and D12, Recolonized D33 | 12 Percentage of participants |
| Total | 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 | PC neg. D12, NC neg. D7, Recolonized D12 | 5 Percentage of participants |
| Total | 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 | PC neg. D33, NC neg. D7, Recolonized D12 | 6 Percentage of participants |
| Total | 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 | PC neg. D12, NC neg. D7 and D12, Recolonized D33 | 17 Percentage of participants |
Secondary
Plasma Retapumulin Pharmacokinetic Parameters by Treatment at 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.
Time frame: Day 5
Population: Per Protocol Population of Intent-to-treat
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Retapamulin 5 Days | Plasma Retapumulin Pharmacokinetic Parameters by Treatment at Day 5 | 2.4118 hours | Standard Deviation 2.48003 |
Secondary
Plasma Retapumulin Pharmacokinetic Parameters, Tmax, by Treatment at 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.
Time frame: Days 1 and 3
Population: Per Protocol Population of Intent-to-treat
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Retapamulin 3 Days | Plasma Retapumulin Pharmacokinetic Parameters, Tmax, by Treatment at Days 1 and 3 | Day 1, n=10 and 3 | 5.6000 hours | Standard Deviation 3.72529 |
| Retapamulin 3 Days | Plasma Retapumulin Pharmacokinetic Parameters, Tmax, by Treatment at Days 1 and 3 | Day 3, n=16 and 10 | 3.8156 hours | Standard Deviation 2.26213 |
| Retapamulin 5 Days | Plasma Retapumulin Pharmacokinetic Parameters, Tmax, by Treatment at Days 1 and 3 | Day 3, n=16 and 10 | 2.4520 hours | Standard Deviation 1.49694 |
| Retapamulin 5 Days | Plasma Retapumulin Pharmacokinetic Parameters, Tmax, by Treatment at Days 1 and 3 | Day 1, n=10 and 3 | 6.9933 hours | Standard Deviation 5.54812 |
Secondary
Prevalence of S. Aureus Nasal and Pharyngeal Carriage by Visit.
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.
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
Population: Screening Population (participants who had anterior nares swab obtained for S. aureus culture) was analyzed for Screening Visit (SV) 1. Only subjects who had positive cultures for S. aureus at SV 1 were allowed to continue to SV 2 and 3. The Safety Population (participants who received at least one dose of study drug) was analyzed at Day 1.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Retapamulin 3 Days | Prevalence of S. Aureus Nasal and Pharyngeal Carriage by Visit. | Screening 1, n=430, 429 | 135 participants |
| Retapamulin 3 Days | Prevalence of S. Aureus Nasal and Pharyngeal Carriage by Visit. | Screening 2, n =104, 92 | 89 participants |
| Retapamulin 3 Days | Prevalence of S. Aureus Nasal and Pharyngeal Carriage by Visit. | Screening 3, n=92 and 58 | 74 participants |
| Retapamulin 3 Days | Prevalence of S. Aureus Nasal and Pharyngeal Carriage by Visit. | Day 1, n=58 and 58 | 53 participants |
| Retapamulin 5 Days | Prevalence of S. Aureus Nasal and Pharyngeal Carriage by Visit. | Day 1, n=58 and 58 | 37 participants |
| Retapamulin 5 Days | Prevalence of S. Aureus Nasal and Pharyngeal Carriage by Visit. | Screening 1, n=430, 429 | 150 participants |
| Retapamulin 5 Days | Prevalence of S. Aureus Nasal and Pharyngeal Carriage by Visit. | Screening 3, n=92 and 58 | 0 participants |
| Retapamulin 5 Days | Prevalence of S. Aureus Nasal and Pharyngeal Carriage by Visit. | Screening 2, n =104, 92 | 0 participants |
Other Pre-specified
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
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.
Time frame: Days 7, 12, and 33.
Population: Per Protocol Population: Persistant Carriers of the Intent-to-Treat (ITT) Population who Tested Positive on Screening Visit 1, 2, 3, and those who were Positive for Pharynegeal Carriage on Day 12 and Day 33 then recolonized.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Retapamulin 3 Days | 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 | PC pos. D12, NC neg. D7, Recolonized D12 | 0 Percentage of participants |
| Retapamulin 3 Days | 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 | PC pos. D33, NC neg. D7 and D12, Recolonized D33 | 40 Percentage of participants |
| Retapamulin 3 Days | 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 | PC pos. D12, NC neg. D7 and D12, Recolonized D33 | 33 Percentage of participants |
| Retapamulin 3 Days | 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 | PC pos. D33, NC neg. D7, Recolonized D12 | 17 Percentage of participants |
| Retapamulin 5 Days | 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 | PC pos. D12, NC neg. D7 and D12, Recolonized D33 | 0 Percentage of participants |
| Retapamulin 5 Days | 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 | PC pos. D33, NC neg. D7 and D12, Recolonized D33 | 25 Percentage of participants |
| Retapamulin 5 Days | 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 | PC pos. D33, NC neg. D7, Recolonized D12 | 17 Percentage of participants |
| Retapamulin 5 Days | 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 | PC pos. D12, NC neg. D7, Recolonized D12 | 33 Percentage of participants |
| Placebo | 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 | PC pos. D12, NC neg. D7 and D12, Recolonized D33 | 0 Percentage of participants |
| Placebo | 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 | PC pos. D12, NC neg. D7, Recolonized D12 | 50 Percentage of participants |
| Placebo | 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 | PC pos. D33, NC neg. D7, Recolonized D12 | 0 Percentage of participants |
| Placebo | 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 | PC pos. D33, NC neg. D7 and D12, Recolonized D33 | 0 Percentage of participants |
| Total | 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 | PC pos. D33, NC neg. D7 and D12, Recolonized D33 | 30 Percentage of participants |
| Total | 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 | PC pos. D33, NC neg. D7, Recolonized D12 | 15 Percentage of participants |
| Total | 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 | PC pos. D12, NC neg. D7 and D12, Recolonized D33 | 22 Percentage of participants |
| Total | 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 | PC pos. D12, NC neg. D7, Recolonized D12 | 18 Percentage of participants |