Treatment of Refractory Chronic Cough With PA101

Treatment of Chronic Idiopathic Cough and Chronic Cough in Patients With Idiopathic Pulmonary Fibrosis With PA101

This is a double-blind, randomized, placebo-controlled, 2-period crossover, 2-cohort study in adult patients with refractory chronic cough.

The purpose of the study is to assess the efficacy and safety of inhaled PA101 delivered via eFlow high efficiency nebulizer for treating refractory chronic cough.

Study Overview

• Status: Completed
• Conditions: Refractory Chronic Cough
• Intervention / Treatment: Drug: Placebo; Drug: PA101

Detailed Description

The study consists of 2 treatment cohorts with refractory chronic cough: Idiopathic Pulmonary Fibrosis (IPF, Cohort 1) and Chronic Idiopathic Cough (CIC, Cohort 2). In each cohort, the study will include two treatment periods of 14 days each separated by a Washout Period of 14 days between Period 1 and Period 2. The two periods will be identical except that in Period 2, patients will crossover to the alternate treatment from that received in Period 1, according to a 1:1 randomization scheme.

During each period, patients will self-administer study drug (i.e., 40 mg PA101 or Placebo PA101 via eFlow) three times daily for 14 consecutive days of each period. Objective cough count will be recorded over 24-hour period using a cough count device (Leicester Cough Monitor) at the Baseline, Day 7 and Day 14 of each treatment period.

In the IPF cohort, patients will be allowed to use antifibrotic therapy (i.e., pirfenidone, nintedanib, and N-acetylcysteine) during the course of the study provided that the dose is stabilized at least 3 months prior to Screening and throughout the study period.

Clinical safety assessments will be performed at the start and end of each treatment period.

• Study Type: Interventional
• Enrollment (Actual): 52
• Phase: Phase 2

Contacts and Locations

Study Locations

• Netherlands
  • Rotterdam, Netherlands
    • Erasmus Medical Center
  • Zwolle, Netherlands
    • Isala
• United Kingdom
  • Leicester, United Kingdom
    • Uni Hospital Leicester
  • London, United Kingdom
    • King's College Hospital
  • London, United Kingdom
    • Royal Brompton & Harefield hospital
  • Stoke-on-Trent, United Kingdom
    • Uni Hospital North Staffordshire
  • East Yorkshire
    • Cottingham, East Yorkshire, United Kingdom
      • Hull Clinical Trials Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis of Idiopathic Pulmonary Fibrosis (based on presence of definitive or possible usual interstitial pneumonia UIP pattern on high-resolution computed tomography and after excluding lung diseases associated with environmental and occupational exposure, with connective tissue disease and with drugs; transfer capacity for carbon monoxide corrected for hemoglobin [TLCOc] >25% predicted within 12 months of Screening; and forced vital capacity [FRC] >50% predicted within 1 month of Screening) or Chronic Idiopathic Cough (that is unresponsive to targeted treatment for identified underlying triggers including post-nasal drip, asthmatic/non-asthmatic eosinophilic bronchitis, and gastro-esophageal reflux disease)
• Refractory chronic cough for at least 8 weeks
• Daytime cough severity score >40 mm on Cough Severity VAS at Screening
• Daytime average cough count ≥15 per hour at Screening
• Willing and able to provide written informed consent

Exclusion Criteria:

• Current or recent history of clinically significant medical condition, laboratory abnormality or illness that could put the patient at risk or compromise the quality of the study data as determined by the investigator
• Upper or lower respiratory tract infection within 4 weeks of Screening
• History of malignancy treated or untreated within the past 5 years, with the exception of localized basal cell carcinoma or cervix carcinoma in situ
• Current or recent history (within 12 months) of excessive use or abuse of alcohol
• Current or recent history (within 12 months) of abusing legal drugs or use of illegal drugs or substances
• Participation in any other investigational drug study within 4 weeks of Screening
• Use of prednisone, narcotic antitussives, baclofen, gabapentin, inhaled corticosteroids, benzonatate, dextromethorphan, carbetapentane, H1 antihistamines, leukotriene modifiers, and cromolyn sodium within 2 weeks of Screening
• Pregnant or breastfeeding females, or if of child-bearing potential unwilling to practice acceptable means of birth control or abstinence during the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PA101; PA101, 40 mg administered via inhalation three times daily for 14 days	Drug: Placebo; Drug: PA101
Placebo Comparator: Placebo; Placebo PA101, administered via inhalation three times daily for 14 days	Drug: Placebo; Drug: PA101

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
cough frequency	objective 24-hour cough monitoring	14 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
cough severity	VAS scale for cough severity	14 days
cough-related quality of life	Leicester Cough Questionnaire	14 days

Collaborators and Investigators

• Sponsor: Patara Pharma

Publications and helpful links

General Publications

• Birring SS, Wijsenbeek MS, Agrawal S, van den Berg JWK, Stone H, Maher TM, Tutuncu A, Morice AH. A novel formulation of inhaled sodium cromoglicate (PA101) in idiopathic pulmonary fibrosis and chronic cough: a randomised, double-blind, proof-of-concept, phase 2 trial. Lancet Respir Med. 2017 Oct;5(10):806-815. doi: 10.1016/S2213-2600(17)30310-7. Epub 2017 Sep 8.

Study record dates

Study Major Dates

• Study Start: February 1, 2015
• Primary Completion (Actual): January 1, 2016
• Study Completion (Actual): February 1, 2016

Study Registration Dates

• First Submitted: April 3, 2015
• First Submitted That Met QC Criteria: April 3, 2015
• First Posted (Estimate): April 8, 2015

Study Record Updates

• Last Update Posted (Estimate): February 22, 2016
• Last Update Submitted That Met QC Criteria: February 18, 2016
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Signs and Symptoms, Respiratory; Cough
• Other Study ID Numbers: PA101-CC-02