A Single-Centre, Open-label, Exploratory Study of the Effect of 20 mg Ambroxol Hydrochloride on Cough Reflex Sensitivity in Patients With Acute Cough.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 14
- 试验地点
- 1
- 主要终点
- Cough reflex sensitivity
研究概览
简要总结
To assess the effect of a single doses of 20 mg ambroxol hydrochloride on cough reflex sensitivity to citric acid, capsaicin, adenosine triphosphate (ATP) and distilled water in patients with acute cough related to upper respiratory tract infection
详细描述
Cough is the 5th most common presenting complaint in adults. Cough results from the stimulation of two types of afferent pathways whose receptors are located within the airway epithelium. These include rapidly adapting receptors (RARs) and C-fibre receptors. Acute as well as chronic, non-productive cough, which often follow viral upper respiratory tract infection, may result from increased sensitivity of the cough reflex. Relatively little research has been done to gain insight into the mechanisms of cough in health and disease, and to properly evaluate potential antitussive therapies. Indeed, little consensus exists regarding the optimal treatment of acute cough because of the lack of standardised outcome measures for cough. Possibly the most significant clinical need in terms of cough therapy is for the cough associated with an acute upper respiratory tract infection (URTI). Although the cough associated with URTI is often self-limiting and resolves within several days, it undoubtedly accounts for a major proportion of huge worldwide expenditure of over-the-counter (OTC) cough and cold products where patients are still struggling to find an effective medication.
This exploratory study will enable us to identify the cough challenge agent (CCA) that is most sensitive to the effect of ambroxol on cough reflex. This is expected to provide a reproducible response, to use in future studies.
This will be an open label, study in subjects with acute cough associated with URTI.
There will be a Screening/Baseline and combined Treatment visit. Subjects will return approximately 1-4 weeks after their treatment once all symptoms have subsided and the subject is no longer suffering from URTI, for a Follow-up Visit.
Up to 14 subjects with acute cough in relation to a URTI and who meet all entry criteria will be assigned to:
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Be informed of the nature of the study and have provided written informed voluntary consent;
- •Be able to speak, read, and understand English;
- •Be males or females, of any race, between 18 and 80 years of age, inclusive;
- •Subject has an acute cough and other symptoms consistent with a common cold or an acute upper respiratory tract infection (URTI) diagnosis deemed by the investigator based on findings from medical history review, full physical examination and vital signs;
- •The onset of symptoms must be within 72 h of study enrolment;
- •Have a Cough Severity VAS ≥ 40 mm at Screening;
- •Be in good general health (other than URTI) with no clinically relevant abnormalities based on the medical history, physical examination, and 12 lead electrocardiogram;
- •Cough at least twice to all cough challenge Agents - citric acid, capsaicin, ATP and distilled water cough challenges at baseline.
- •If a female of child-bearing potential (i.e., have not undergone a hysterectomy or bilateral oophorectomy) or not post-menopausal (defined as no menses for at least 12 months), agree to use 2 forms of acceptable birth control from Screening through to the Follow Up Visit; or if a male, they and/or their partner of child-bearing potential agree to use 2 forms of acceptable birth control from Screening through the Follow Up Visit;
- •Be able to communicate effectively with the Investigator and other study centre personnel and agree to comply with the study procedures and restrictions.
排除标准
- •History of asthma or other respiratory related disease
- •Symptoms of runny nose, stuffy nose, sore throat, or sneezing due to any condition other than URTI or common cold (e.g., seasonal or perennial allergic rhinitis, sinusitis, strep throat, vasomotor rhinitis, etc.) as established by the investigator
- •Clinical features of a complication of the common cold during the physical examination at screening (e.g., otitis media, sinusitis, or pneumonia) with or without the need for systemic antibiotics
- •History of a severe cutaneous adverse reaction to any treatment;
- •Evidence of a possible bacterial infection i.e. sinus pain, purulent nasal discharge or pleuritic pain.
- •Evidence of chest infection or pneumonia
- •Fever greater than 39ºC (102ºF oral temperature) at the time of screening if, in the judgment of the investigator, the individual is too ill to participate in the study or the fever is due to reasons other than URTI
- •Demonstrate more than two coughs to inhalation of the normal saline solution during baseline challenge
- •Current smoker or individuals who have given up smoking within the past 6 months or those with >20 pack-year smoking history;
- •Treatment with an ACE-inhibitor during the study or within 4 weeks prior to Screening
- •History of opioid use within 1 week prior to baseline;
- •Requiring concomitant therapy with prohibited medications
- •History of known or suspected allergy or hypersensitivity reactions to ambroxol (e.g., asthma, urticaria or allergic type) or any of the non-medicinal ingredients contained in the study investigational product.
- •Clinically significant abnormal electrocardiogram (ECG) at Screening;
- •Personal or family history of congenital long QT syndrome or family history of sudden death;
- •Pregnant or breastfeeding;
- •Treatment with an investigational drug or biologic within 30 days preceding the first dose of study medication or plans to take another investigational drug or biologic within 30 days of study completion;
- •Other severe, acute, or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with trial participation or investigational product administration or may interfere with the interpretation of trial results and, in the judgment of the Investigator or Sponsor, would make the subject inappropriate for entry into this trial -
研究组 & 干预措施
20 mg ambroxol
20 mg ambroxol lozenge delivered once on one day
干预措施: Ambroxol Hydrochloride (Drug)
结局指标
主要结局
Cough reflex sensitivity
时间窗: 8 hours
To assess the effect of single dose of 20 mg ambroxol lozenge on cough reflex sensitivity (quatified by recording the concenteration of cough stimulant evoking 2 (C2) and 5 (C5 ) coughs) to four different types of challenge agents in acute cough associated with URTI.
次要结局
- Severity of cough Visual analogue scale (VAS)(90 min post dose)
- Urge to cough Visual analogue scale (VAS)(90 min post dose)
- Change in cough reflex sensitivity from during acute cough to post symptom recovery(up tp 1 month)