Cough Reduction in IPF With Nalbuphine ER (CORAL)
|
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT05964335 |
|
Recruitment Status :
Recruiting
First Posted : July 27, 2023
Last Update Posted : May 14, 2024
|
Sponsor:
Trevi Therapeutics
Information provided by (Responsible Party):
Trevi Therapeutics
- Study Details
- Tabular View
- No Results Posted
- Disclaimer
- How to Read a Study Record
Brief Summary:
This is a multi-center randomized, double-blind, placebo-controlled, parallel, 4-arm study of nalbuphine ER (NAL ER).
After meeting eligibility during the Screening Period, subjects will be randomized (1:1:1:1) to one of four treatment arms.
- Arm 1: Placebo
- Arm 2: 27 mg nalbuphine ER
- Arm 3: 54 mg nalbuphine ER
- Arm 4: 108 mg nalbuphine ER
Each arm will be titrated to their fixed dose during the blinded 2-week Titration period followed by the 4-week Fixed Dose Period for a total of 6 weeks on drug.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Idiopathic Pulmonary Fibrosis | Drug: nalbuphine ER 27 mg Drug: Placebo Drug: nalbuphine ER 54 mg Drug: nalbuphine ER 108 mg | Phase 2 |
This is a multi-center randomized, double-blind, placebo-controlled, parallel, 4-arm study.
After meeting eligibility during the Screening Period, subjects will be randomized (1:1:1:1) to one of four treatment arms.
- Arm 1: Placebo
- Arm 2: 27 mg nalbuphine ER
- Arm 3: 54 mg nalbuphine ER
- Arm 4: 108 mg nalbuphine ER
Each arm will be titrated to their fixed dose during the blinded 2-week Titration period according to Table: Dosing Scheme, followed by the 4-week Fixed Dose Period for a total of 6 weeks on drug.
Subjects will be taken off study drug at the end of the Fixed Dose Period and followed off treatment for an additional 2 weeks.
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 160 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Double (Participant, Investigator) |
| Primary Purpose: | Treatment |
| Official Title: | A Randomized, Double-Blind, Placebo-Controlled, Parallel, 4-Arm Dose Ranging Study of the Safety and Efficacy of Nalbuphine Extended-Release Tablets (NAL ER) for the Treatment of Cough in Idiopathic Pulmonary Fibrosis (IPF) |
| Actual Study Start Date : | February 6, 2024 |
| Estimated Primary Completion Date : | October 1, 2024 |
| Estimated Study Completion Date : | October 14, 2024 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Idiopathic pulmonary fibrosis
| Arm | Intervention/treatment |
|---|---|
|
Experimental: NAL ER 27 mg
BID
|
Drug: nalbuphine ER 27 mg
Oral tablets
Other Name: Active |
|
Experimental: NAL ER 54 mg
BID
|
Drug: nalbuphine ER 54 mg
Oral Tablets
Other Name: Active |
|
Experimental: NAL ER 108 mg
BID
|
Drug: nalbuphine ER 108 mg
Oral tablets
Other Name: Active |
|
Placebo Comparator: Placebo
Placebo, tablets BID
|
Drug: Placebo
Oral tablets |
Primary Outcome Measures :
- Effect of NAL ER on 24-hour cough frequency (coughs per hour) [ Time Frame: Week 6 ]Relative change from Baseline in 24-hour cough frequency versus placebo
Secondary Outcome Measures :
- Effect of NAL ER on the EXAcerbation of Chronic pulmonary disease Tool [ Time Frame: Week 6 ]Relative change from Baseline in the EXACT© question 2 at Week 6 versus placebo
- Safety and tolerability of NAL ER [ Time Frame: Screening through 14 day post last dose ]Adverse event, vitals signs, ECGs, clinical laboratory tests, spirometry, physical examinations, Subjective Opiate Withdrawal Scale (SOWS)
- 24-hour cough frequency (Coughs per hour) [ Time Frame: Weeks 2, 4, 6 ]
Relative change from Baseline in 24-hour cough frequency (coughs per hour) versus placebo
• Proportion of responders with ≥30%, ≥50% and ≥75% reduction in the 24-hour cough frequency at Week 2, 4, and 6, for NAL ER compared with placebo.
- Awake cough frequency (Coughs per hour) [ Time Frame: Weeks 2, 4, 6 ]Relative change from Baseline in awake cough frequency (coughs per hour) versus placebo.
- Sleep cough frequency (Coughs per hour) [ Time Frame: Weeks 2, 4, 6 ]Relative change from Baseline in sleep cough frequency (coughs per hour) at versus placebo.
- EXACT© (EXAcerbation of Chronic pulmonary disease Tool) (EXAcerbation of Chronic pulmonary disease Tool) [ Time Frame: Weeks 1, 2, 3, 4, 5, 6 ]Change from Baseline in the EXACT© question 2 compared with placebo. Proportion of EXACT© question 2 responders, with response defined as at least a one category improvement versus placebo. Change from Baseline in the EXACT© sub-domains and individual items versus placebo.
- CS-NRS (Cough Severity Numerical Rating Scale) [ Time Frame: Weeks 1, 2, 3, 4, 5, 6 ]Change from Baseline in the CS-NRS versus placebo.
- LCQ© (Leicester Cough Questionnaire) [ Time Frame: Week 6 ]Change from Baseline in the LCQ© total score versus placebo. Proportion of LCQ© responders, with response defined as 1.3-point increase versus placebo
- L-IPF© (Living with Pulmonary Fibrosis Impacts Questionnaire) [ Time Frame: Week 6 ]Change from Baseline in the L-IPF© versus placebo.
- L-IPF© (Living with Pulmonary Fibrosis Symptoms Questionnaire) [ Time Frame: Week 6 ]Change from Baseline in the L-IPF© versus placebo.
- EQ-5D-5L™ [ Time Frame: Week 6 ]Change from Baseline in the EQ-5D-5L™ versus placebo.
- PGI-S Cough (Patient Global Impression of Severity for Cough) [ Time Frame: Weeks 2, 4, 6 ]1 item measure rating the severity of cough past 7 days from No cough, Mild, Moderate or Severe
- PGI-S IPF (Patient Global Impression of Severity and Change for IPF) [ Time Frame: Weeks 2, 4, 6 ]1 item measure rating the symptoms of IPF past 7 days from No symptoms, Mild, Moderate or Severe
- CGI-S, (Clinicians Global Impression of Severity) [ Time Frame: Baseline and Week 6 ]A one-item measure evaluating severity of the condition. No Symptoms Mild Moderate Severe
- PGI-C Cough; (Patient Global Impression of Change for Cough) [ Time Frame: Weeks 2, 4, 6 ]
1 item measure rating the symptoms of IPF. (past 7 days)
- Much better
- Moderately better
- A little better
- No change
- A little worse
- Moderately worse
- Much worse
- PGI-C IPF (Patient Global Impression of Change in IPF symptoms) [ Time Frame: Weeks 2, 4, 6 ]
1 item measure rating the symptoms of IPF. (Past 7 days)
- Much better
- Moderately better
- A little better
- No change
- A little worse
- Moderately worse
- Much worse
- CGI-C [ Time Frame: Week 6 ]
A one-item measure evaluating change from the initiation of treatment on a seven point scale.
- = Very much improved
- = Much improved
- = Minimally improved
- = No change
- = Minimally worse
- = Much worse
- = Very much worse
Information from the National Library of Medicine
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Diagnosis of IPF as determined by the Principal Investigator based on ATS/ERS/JRS/ALAT guidelines.
- Cough Severity Score ≥ 4 on CS-NRS (Cough Severity Numerical Rating Scale) during the Screening period and Baseline.
- History of chronic cough for at least 8 weeks before screening.
- SpO2 ≥ 92%, taken after at least 5 minutes in a sitting position, undisturbed and non-stimulated (Saturation of Hemoglobin with Oxygen as Measured by Pulse Oximetry).
- FVC ≥ 40% predicted of normal - Forced Vital Capacity, as determined by spirometry adhering to ATS/ERS guidelines.
- DLCO ≥ 25% predicted of normal - Diffusing capacity of the lung for carbon monoxide corrected for hemoglobin, assessed within the last 12 weeks, or at the time of screening.
Exclusion Criteria:
- Currently on continuous oxygen therapy for longer than 16 hours at any level or delivered by any modality. Intermittent oxygen use of any duration over any given 24-hour period is allowed.
- Inadequate swallow reflex as assessed by the ability to sip 3 fluid oz (or 89 mL) of water without coughing or choking.
- Upper or lower respiratory tract infection in the last 8 weeks prior to the baseline visit.
- Clinical history of aspiration pneumonitis.
- Diagnosis of sleep apnea.
- Abnormal kidney or liver functions based on Screening lab results.
- Known hypersensitivity to nalbuphine or to NAL ER excipients
- History of major psychiatric disorder.
- History of substance abuse.
- Significant medical condition or other factors that may interfere with the subject's ability to successfully complete the study.
- Pregnant or lactating female subject.
- Known intolerance (gastrointestinal, central nervous system symptoms), hypersensitivity, drug allergy following the use of an opioid drug.
- Use of opiates is prohibited within 14 days prior to the baseline visit.
- Use of benzodiazepines are prohibited within 14 days prior to the baseline visit and for the duration of the study.
- Monoamine oxidase inhibitors (MAOIs) including methylene blue (methylthioninium chloride) and the antibiotic linezolid are prohibited within 14 days prior to the baseline visit and for the duration of the study.
- Use of oral corticosteroid cough treatment is prohibited within 4 weeks prior to the baseline visit and for the duration of the study.
- Exposure to any investigational medication, including placebo, is prohibited within 4 weeks prior to the baseline visit and for the duration of the study.
- Medications prescribed as cough suppressants are prohibited unless on a stable dose 14-days prior to the baseline visit and are expected to remain on that dose for the duration of the study.
- Use of medications that affect serotonergic neurotransmission and that when used concomitantly with opioids can increase the risk of serotonin syndrome are prohibited unless on a stable dose 14-days prior to the baseline visit and are expected to remain on that dose for the duration of the study.
- Anti-fibrotic medications are prohibited unless on a stable dose for 8 weeks prior to the baseline visit and are expected to remain on that dose for the duration of the study.
- Strong inhibitors/inducers of the P450 Isozymes are prohibited unless on a stable dose for 14-days prior to baseline visit and are expected to remain on that dose for the duration of the study.
- Use of a medication having a "known risk" of Torsade de Pointes (categorized as "KR" on the Credible Meds® website.) 4 weeks prior to Baseline.
- Use of unstable doses of medications associated with a potential risk of QT prolongation but not clearly associated with Torsade de Pointes within 4 weeks of screening.
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05964335
Contacts
| Contact: Beata Dworakowska | 203-654-3284 | Beata.Dworakowska@trevitherapeutics.com | |
| Contact: Catherine Weenink | 203-684-2560 | Catherine.Weenink@trevitherapeutics.com |
Locations
Show 63 study locations
Sponsors and Collaborators
Trevi Therapeutics
Investigators
| Study Director: | David Clark, MD | Trevi Therapeutics |
| Responsible Party: | Trevi Therapeutics |
| ClinicalTrials.gov Identifier: | NCT05964335 |
| Other Study ID Numbers: |
NAL03-202 |
| First Posted: | July 27, 2023 Key Record Dates |
| Last Update Posted: | May 14, 2024 |
| Last Verified: | May 2024 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
| Product Manufactured in and Exported from the U.S.: | Yes |
Keywords provided by Trevi Therapeutics:
|
Cough Nalbuphine |
Additional relevant MeSH terms:
|
Pulmonary Fibrosis Idiopathic Pulmonary Fibrosis Fibrosis Pathologic Processes Lung Diseases, Interstitial Lung Diseases Respiratory Tract Diseases Nalbuphine |
Analgesics, Opioid Narcotics Central Nervous System Depressants Physiological Effects of Drugs Analgesics Sensory System Agents Peripheral Nervous System Agents |