Last updated: 08/30/2021 22:50:22
A study to assess the effectiveness and side effects of GSK2798745 in participants with chronic cough
EudraCT ID
EU CT Number
Not applicable
Trial status
Other
Other
Trial overview
Official title: A placebo-controlled, double-blind (sponsor open), randomized, crossover study to assess the efficacy, safety, and tolerability of GSK2798745 in participants with chronic cough
Trial description: GSK2798745 is a potent and selective transient receptor potential vanilloid 4 (TRPV4) channel blocker being investigated for the treatment of chronic cough. This is a multi-center, randomized, placebo-controlled, double-blind, two-period crossover study with a purpose to evaluate efficacy and safety of GSK2798745. Each subject will have 2 treatment periods, and will be randomized to one of the following treatments in each period: A) Placebo matching to GSK2798745 once daily for 7 days. B) 4.8 milligrams (mg) GSK2798745 on Day 1, followed by 2.4 mg GSK2798745 once daily for 6 days. There will be a washout period of 14 to 21 days between the treatment periods. A maximum of 48 subjects will be enrolled in the study and the total duration of participation in the study will be maximum of 10 and a half weeks including follow-up visit.
Primary purpose:
Treatment
Trial design:
Crossover Assignment
Masking:
Double (Participant, Investigator)
Allocation:
Randomized
Primary outcomes:
Number of coughs during day-time hours following 7 days of dosing
Timeframe: Up to 35 days
Secondary outcomes:
Number of subjects with adverse events (AE) and serious adverse events (SAE)
Timeframe: Up to 45 days
Number of subjects with abnormal hematology parameters
Timeframe: Up to 45 days
Number of subjects with abnormal clinical chemistry parameters
Timeframe: Up to 45 days
Number of subjects with abnormal urinalysis parameters
Timeframe: Up to 45 days
Number of subjects with abnormal values of cardiac troponin
Timeframe: Up to 45 days
Number of subjects with abnormal systolic blood pressure (SBP) and diastolic blood pressure (DBP)
Timeframe: Up to 45 days
Number of subjects with abnormal heart rate
Timeframe: Up to 45 days
Number of subjects with abnormal temperature
Timeframe: Up to 45 days
Number of subjects with abnormal electrocardiogram (ECG) findings
Timeframe: Up to 45 days
Interventions:
Enrollment:
17
Primary completion date:
2018-08-10
Observational study model:
Not applicable
Time perspective:
Not applicable
Clinical publications:
V Ludbrook, K Hanrott, J Kreindler, J Marks-Konczalik, N Bird, D Hewens, M Beerahee, D Behm, L McGarvey, A Morice, S Parker,S. Birring, J Smith. An adaptive study design to assess the efficacy, safety and tolerability of TRPV4 inhibitor GSK2798745 in participants with idiopathic or refractory chronic cough. ERJ Open Res. 2021;7(00269-2021)
DOI: 10.1183/23120541.00269-202
Medical condition
Cough
Product
GSK2798745
Collaborators
BARDA (Biomedical Advanced Research and Development Authority)
Study date(s)
April 2018 to October 2018
Type
Interventional
Phase
2
Participation criteria
Sex
Female & Male
Age
18 - 75 years
Accepts healthy volunteers
No
- Age between 18 and 75 years of age inclusive, at the time of signing the informed consent.
- Chronic idiopathic cough for >=1 year (before screening), defined as: a cough that is unresponsive to at least 8 weeks of targeted treatment, or a cough for which no objective evidence of an underlying trigger has been determined, despite medical investigations.
- History or current evidence of any serious or clinically significant gastrointestinal, renal, endocrine, neurologic, hematologic or other condition that is uncontrolled on permitted therapies or that would, in the opinion of the investigator or the medical monitor, make the subject unsuitable for inclusion in this study.
- History or current evidence of chronic productive cough.
Inclusion and exclusion criteria
Inclusion criteria:
- Age between 18 and 75 years of age inclusive, at the time of signing the informed consent.
- Chronic idiopathic cough for >=1 year (before screening), defined as: a cough that is unresponsive to at least 8 weeks of targeted treatment, or a cough for which no objective evidence of an underlying trigger has been determined, despite medical investigations.
- No significant findings on chest imaging (chest X-ray [CXR] or Computed tomography scan) within 12 months before screening (subjects with an abnormal CXR within 12 months, from a temporary process, will be allowed to participate if a repeat CXR is normal).
- Forced expiratory volume in one second (FEV1) >=80% of the predicted normal value (at screening), or documented evidence of FEV1 >=80% within the 6 months before screening.
- Score of >=40 millimeters (mm) on the Cough Severity Visual Analogue Scale (VAS) at Screening.
- Body weight >=50 kilogram (kg) and body mass index (BMI) within the range 18 to 40 kilogram per meter square (kg/m^2) (inclusive) at screening.
- A male participant must agree to follow the contraception requirements stated in the protocol from the time of first dose of study treatment until 2 weeks after last dose of study treatment, and refrain from donating sperm during this period.
- A female participant is eligible to participate if she is not of childbearing potential.
- Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
Exclusion criteria:
- History or current evidence of any serious or clinically significant gastrointestinal, renal, endocrine, neurologic, hematologic or other condition that is uncontrolled on permitted therapies or that would, in the opinion of the investigator or the medical monitor, make the subject unsuitable for inclusion in this study.
- History or current evidence of chronic productive cough.
- History of acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting within the 6 months before screening.
- Active ulcer disease or gastrointestinal bleeding at the time of screening (positive fecal occult blood test [FOBT] at screening).
- History of stroke or seizure disorder within 5 years of screening.
- Respiratory tract infection within 6 weeks of screening.
- Subject who, in the investigator’s opinion, poses a significant suicide risk. Evidence of serious suicide risk may include any history of suicidal behavior and/or any evidence of suicidal ideation on any questionnaires e.g. Type 4 or 5 on the Columbia Suicidality Severity Rating Scale (C-SSRS) in the last 6 months (assessed at screening).
- Alanine transferase (ALT) > twice the upper limit of normal (ULN) at screening.
- Bilirubin >1.5 times ULN (isolated bilirubin >1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%) at screening.
- Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
- QT interval corrected (QTc) >450 milliseconds (msec) or QTc >480 msec in subjects with bundle branch block at screening.
- Use of a listed prohibited medication within the restricted timeframe relative to the first dose of study treatment.
- Use of a strong inhibitors or inducers of cytochrome P450 (CYP) 3A or pglycoprotein.
- Participation in the study would result in loss of blood or blood products in excess of 500 milliliters (mL) within 3 months of screening.
- Exposure to more than 4 new chemical entities within 12 months prior to the first dosing day.
- Current enrollment or past participation within the 3 months before screening in any clinical study involving an investigational study treatment or any other type of medical research.
- Positive human immunodeficiency virus (HIV) antibody test at screening.
- Presence of Hepatitis B surface antigen (HBsAg) at screening.
- Positive Hepatitis C antibody test result at screening or within 3 months prior to starting study treatment.
- Positive Hepatitis C ribonucleic acid (RNA) test result at screening or within 3 months prior to first dose of study treatment.
- Cardiac troponin at screening > ULN for the assay.
- History of alcohol abuse within 6 months of screening, in the opinion of the investigator.
- Current smoker or history of smoking within the 6 months before screening, or a cumulative history of >= 20 pack years. Pack years = (Number of cigarettes smoked/day/20) x (Number of years smoked)
- Sensitivity to any of the study treatments, or components thereof, or drug or other allergy that, in the opinion of the investigator or Medical Monitor, contraindicates participation in the study.
Trial location(s)
Location
GSK Investigational Site
Cottingham, East Yorkshire, United Kingdom, HU16 5JQ
Status
Study Complete
Location
GSK Investigational Site
Manchester, Lancashire, United Kingdom, M23 9LT
Status
Study Complete
Location
GSK Investigational Site
North Shields, United Kingdom, NE29 8NH
Status
Study Complete
Study documents
Protocol
Available language(s): English
Statistical analysis plan
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Results posted on ClinicalTrials.gov
Recruitment status
Other
Actual primary completion date
2018-08-10
Actual study completion date
2018-08-10
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
Additional information about the trial
Additional information
Not applicable
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