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
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 57
- 试验地点
- 1
- 主要终点
- Plasma Retapumulin Pharmacokinetic Parameters by Treatment at Days 1 and 3 Evaluated by Plasma AUC After Dosing
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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/m
- •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.
排除标准
- •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.
研究组 & 干预措施
Treatment B
200mg BID retapamulin 5 days
干预措施: Retapamulin (Drug)
Treatment C
200mg BID placebo 5 days
干预措施: Placebo (Drug)
Treatment A
200mg BID retapamulin 3 days and placebo BID 2 days for a total of 5 days
干预措施: Retapamulin (Drug)
结局指标
主要结局
Plasma Retapumulin Pharmacokinetic Parameters by Treatment at Days 1 and 3 Evaluated by Plasma AUC After Dosing
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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.
次要结局
- Plasma Retapumulin Pharmacokinetic Parameters, Tmax, by Treatment at Days 1 and 3(Days 1 and 3)
- 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 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)
- Plasma Retapumulin Pharmacokinetic Parameters by Treatment at Day 5(Day 5)
- 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)
- Number of Participants With a Nasal Culture Negative for MRSA (Methicillin-resistant S. Aureus)(Days 7, 12, or 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)