A Study to Assess the Effectiveness and Side Effects of GSK2798745 in Participants With Chronic Cough

NCT03372603 | Terminated Phase 1 Results

• 2 other identifiers: 2077022017-002265-21
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 8

Brief Summary

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.

Conditions

Cough

Keywords

GSK2798745, efficacy, safety, chronic cough, crossover study

Outcome Measures

Primary Outcomes (1)

• Total Cough Counts During Day Time Hours Following 7-days of Dosing

  Coughs were monitored using the VitaloJAK cough monitor. The total cough counts during day-time (10 hours) was calculated from the time of the monitor being attached i.e. immediately after dosing on Day 7 to 10 hours past the time of monitoring. Total cough counts were log-transformed prior to analysis. A non-informative prior was used. Analysis was performed using a Bayesian mixed model adjusting for subject-level and period-adjusted baselines, treatment and period. Subject-level baseline is defined as the mean of the two period-specific baselines. Period-adjusted baseline is defined as the difference between the period-specific baseline and subject-level baseline for each period. Posterior median and 95% credible interval is reported. All Subjects Population included all randomized participants who took at least 1 dose of study treatment. Participants were analyzed according to the treatment they actually received.

  Up to 10 hours post-dose on Day 7 of each treatment period

Secondary Outcomes (18)

• Number of Participants Reporting Adverse Events (AEs) and Serious Adverse Events (SAEs)

  Up to 45 days

• Change From Baseline Values for Clinical Chemistry Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Amino Transferase (AST) and Creatinine Kinase (CK)

  Baseline (Day -1) and Day 8 of each treatment period

• Change From Baseline Values for Clinical Chemistry Parameter: Direct Bilirubin, Total Bilirubin and Creatinine

  Baseline (Day -1) and Day 8 for each treatment period

• Change From Baseline Values for Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Urea

  Baseline (Day -1) and Day 8 of each treatment period

• Change From Baseline Values for Clinical Chemistry Parameter: Total Protein

  Baseline (Day -1) and Day 8 of each treatment period

Study Arms (2)

Treatment Sequence AB

EXPERIMENTAL

Subjects will receive GSK2798745 matching placebo tablets (two tablets on Day 1 followed by one tablet once daily for 6 days), via oral route (treatment period of total 7 days). After a washout period of 14 to 21 days, subjects will then receive 4.8 mg (two tablets of 2.4 mg) GSK2798745 on Day 1, followed by 2.4 mg GSK2798745 tablets once daily for 6 days via oral route (treatment period of total 7 days).

Drug: GSK2798745; Drug: Placebo

Treatment Sequence BA

EXPERIMENTAL

Subjects will receive 4.8 mg (two tablets of 2.4 mg) GSK2798745 on Day 1, followed by 2.4 mg GSK2798745 tablets once daily for 6 days via oral route (treatment period of total 7 days). After a washout period of 14 to 21 days, subjects will then receive GSK2798745 matching placebo tablets (two tablets on Day 1 followed by one tablet once daily for 6 days), via oral route (treatment period of total 7 days).

Drug: GSK2798745; Drug: Placebo

Interventions

GSK2798745 DRUG

GSK2798745 tablets will be available as white to almost white, round, film-coated tablets (micronized active pharmaceutical ingredient \[API\]) to be taken with a glass of water (approximately 240 mL).

Treatment Sequence AB; Treatment Sequence BA

Placebo DRUG

Placebo tablets will be available as white to almost white, round, film-coated tablets to be taken with a glass of water (approximately 240 mL).

Treatment Sequence AB; Treatment Sequence BA

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead
• Biomedical Advanced Research and Development Authority: collaborator

Study Sites (8)

GSK Investigational Site

Manchester, Lancashire, M23 9LT, United Kingdom

Location

GSK Investigational Site

Manchester, Lancashire, M23 9L, United Kingdom

Location

GSK Investigational Site

Belfast, BT9 7BL, United Kingdom

Location

GSK Investigational Site

Belfast, BT9 7B, United Kingdom

Location

GSK Investigational Site

Cottingham, HU16 5JQ, United Kingdom

Location

GSK Investigational Site

Cottingham, HU16 5, United Kingdom

Location

GSK Investigational Site

North Shields, NE29 8NH, United Kingdom

Location

GSK Investigational Site

North Shields, NE29 8, United Kingdom

Location

MeSH Terms

Conditions

Cough; Chronic Cough

Interventions

GSK2798745

Condition Hierarchy (Ancestors)

Respiration Disorders; Respiratory Tract Diseases; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

• GSK Clinical Trials

  GlaxoSmithKline (for GlaxoSmithKline; Human Genome Sciences Inc., a GSK Company; Sirtris, a GSK Company; Stiefel, a GSK Company; ViiV Healthcare)

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: All study staff involved in clinical assessments (which includes the investigator, sub-investigators, other site staff), and the subject will be blinded to the treatment allocated to individual subjects.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is a multi-center, randomized, placebo-controlled, double-blind, two-period crossover study. Each subject will be screened (screening may be conducted across more than 1 visit); each subject will have 2 treatment periods (each 7 days) with a washout period of 14 to 21 days between the treatment periods; and each subject will have a follow-up visit (within 7 to 10 days after their last dose). Each subject will be involved in the study for a maximum of 10 and a half weeks.

Study Record Dates

• First Submitted: December 8, 2017
• First Posted: December 13, 2017
• Study Start: April 5, 2018
• Primary Completion: October 8, 2018
• Study Completion: October 8, 2018
• Last Updated: October 2, 2019
• Results First Posted: October 2, 2019

Record last verified: 2019-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints of the study.
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

Locations

GB (8)