TR12 Ph 2 Study in Idiopathic Pulmonary Fibrosis-Nalbuphine ER Tablets
Research type
Research Study
Full title
A Phase 2, Double-blind, Randomized, Placebo-controlled, Two-Treatment, Two-Period Crossover Efficacy and Safety Study in Idiopathic Pulmonary Fibrosis with Nalbuphine ER Tablets for the Treatment of Cough
IRAS ID
262846
Contact name
Toby Maher
Contact email
Sponsor organisation
Trevi Therapeutics, Inc.
Eudract number
2018-004744-31
Duration of Study in the UK
1 years, 0 months, 14 days
Research summary
The purpose of this study is to test whether nalbuphine extended-release (NAL ER) tablets are safe, and whether they work in the treatment of cough, in patients with diagnosed Idiopathic Pulmonary Fibrosis (IPF) who are bothered by coughing associated with this condition. NAL ER tablets will be compared with placebo.
The cause of IPF is often difficult to determine, but it can be highly bothersome and is associated with coughing episodes leading to shortness of breath and exhaustion.
The study will be run in the UK only at 2 sites (approximately 8 additional sites may be opened in the future). Approximately 56 subjects in total will be randomised to ensure evaluable data from at least 44 subjects.
The study will last approximately 12 months from first patient in to last patient out.The study consists of 2 treatment periods of 3 weeks, each followed by a washout period of 2 weeks.
At the start of Treatment Period 1, eligible subjects will be randomized (1:1) to one of the following treatment arms:
• Arm 1: Active NAL ER only in Treatment Period 1 followed by treatment with Placebo only in Treatment Period 2
• Arm 2: Placebo only in Treatment Period 1 followed by treatment with NAL ER only in Treatment Period 2Assessments will include blood and urine sampling for safety testing and blood sampling for determining the level of study drug in patients’ blood (pharmacokinetics), and the completion of questionnaires to determine how severe certain symptoms (for example, cough, breathlessness, fatigue) are. Blood and urine sampling for pregnancy testing will be performed on females of childbearing potential. Patients will also wear a portable cough monitor that will measure how often they cough at times during the study, including at night.
Results Summary
Background
Idiopathic pulmonary fibrosis is a rare, progressive illness. Idiopathic means there is no known cause for this disease. Pulmonary means it affects the lungs. Fibrosis means scar tissue replaces normal tissue in the lungs so they cannot expand normally. So, patients affected by this disorder suffer from the gradual formation of scar tissue in the lungs making it difficult to breathe.
There is no cure for idiopathic pulmonary fibrosis. Patients with this condition suffer from increasing shortness of breath and a dry cough which can become severe. The cough can become so frequent it disrupts daily activities and can become so severe it causes vomiting and even broken ribs. Normal cough medications are not very affective for these patients.
Nalbuphine Extended-Release Tablets.
Trevi Therapeutics is a U.S. pharmaceutical company that is seeking a treatment for cough in patients with idiopathic pulmonary fibrosis. Trevi is testing a drug called Nalbuphine Extended-Release (NAL ER) Tablets.
This medication was tested in a clinical trial called “A Phase 2, Double-Blind, Randomized, Placebo-Controlled, Two-Treatment, Two-Period Crossover Efficacy and Safety Study in Idiopathic Pulmonary Fibrosis with Nalbuphine ER Tablets for the Treatment of Chronic Cough.”
A Phase 2 clinical trial means it involves patients who are living with the illness that the new medication is meant to treat. Randomized means the patients randomly received the new medication or a non-medicated Placebo. Double-Blind means neither the patients nor the physicians knew which treatment everyone had received. This trial was given the code name TR12 and was conducted at 11 sites in the United Kingdom between October 2019 and May 2022.
The TR12 Clinical Trial
The primary goal of TR12 was to study the safety of NAL ER in patients with idiopathic pulmonary fibrosis, and to measure the effectiveness of the drug on the frequency of coughing (coughs per hour) after taking the drug two times daily for 21 days.
Other measures included questionnaires to measure the effects of NAL ER on the quality of life of treated patients. The study included 42 patients suffering from idiopathic pulmonary fibrosis. They were mostly men (85%) with an average age of 74 years.
On Day 1 (baseline), half the patients randomly started treatment with NAL ER and half received placebo. The effectiveness of the treatment was checked after 8, 15 and 21 days. At that time, all patients stopped their treatments during a 2-week “washout” period. Then, the study was continued except patients taking NAL ER were switched to placebo, and patients treated with placebo were switched to NAL ER. The effects of the new treatments were checked again after 8, 15 and 21 days of treatment.
On Day 1 and Day 21 of each treatment period, the frequency of coughing was measured with an electronic cough monitor which was worn for 24 hours. Each patient also completed questionnaires about their symptoms and made daily diary entries to record any side effects from their treatment.
TR12 Clinical Trial Results
After treatment with NAL ER for 21 days, patients had an average 75% decrease in their cough frequency compared to Day 1. Patients treated with placebo only had a 22% decrease. There was also a significant decrease in cough severity among patients when treated with NAL ER. The patients also reported improvements in their symptoms of tiredness, exhaustion, and fatigue. The most common side effects in patients treated with NAL ER were nausea (42%), fatigue (32%), constipation (29%), dizziness (26%), sleepiness (24%), vomiting (18%), dry-mouth (13%), and anxiety (13%). These side effects were generally mild to moderate and there were no serious side effects related to NAL ER.
Conclusions
The results of this trial indicate NAL ER is a potential new treatment for cough in patients with idiopathic pulmonary fibrosis. There were no serious side effects related to NAL ER. Based on these results, further study into the use of NAL ER for the treatment of chronic cough in adults with idiopathic pulmonary fibrosis is warranted.
Acknowledgement
The staff of Trevi Therapeutics and the physicians involved in this study express their gratitude to the patients with idiopathic pulmonary fibrosis for their voluntary participation in this study. Additional information about this study can be found at ClinicalTrials.Gov, available: https://gbr01.safelinks.protection.outlook.com/?url=https%3A%2F%2Ftrack.pstmrk.it%2F3ts%2Fclinicaltrials.gov%252Fstudy%252FNCT04030026.%2FNBTI%2Ftya_AQ%2FAQ%2Fcfd9a397-5c19-4f52-9fef-bacebdf57126%2F2%2Fe5TU0OKwGg&data=05%7C02%7Cgmsouth.rec%40hra.nhs.uk%7Cc072c23daa22465e899208ddb035f9ec%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638860468055627641%7CUnknown%7CTWFpbGZsb3d8eyJFbXB0eU1hcGkiOnRydWUsIlYiOiIwLjAuMDAwMCIsIlAiOiJXaW4zMiIsIkFOIjoiTWFpbCIsIldUIjoyfQ%3D%3D%7C0%7C%7C%7C&sdata=dV29HAHVXtHnJdNqeoXq1WBZYYNOkKQzfNMaByq4F%2Fo%3D&reserved=0REC name
North West - Greater Manchester South Research Ethics Committee
REC reference
19/NW/0317
Date of REC Opinion
24 Jun 2019
REC opinion
Favourable Opinion