Haduvio (nalbuphine ER) / Trevi Therap, Endo - LARVOL DELTA

A Food Effect Study to Evaluate the Relative Bioavailability of Nalbuphine Extended-Release Tablets (NAL ER) in Healthy Participants (clinicaltrials.gov) - P1 | N=60 | Recruiting | Sponsor: Trevi Therapeutics

New P1 trial

Study of Nalbuphine ER in Participants With Hepatic Impairment (clinicaltrials.gov) - P1 | N=28 | Completed | Sponsor: Trevi Therapeutics | Active, not recruiting ➔ Completed | N=56 ➔ 28

Enrollment change • Trial completion • Hepatology

Trevi Therapeutics Announces Completion of End-of-Phase 2 Meeting with the FDA, Gaining Alignment for Its Development Program for Idiopathic Pulmonary Fibrosis-Related Chronic Cough (GlobeNewswire) - " At the meeting, the Company gained overall alignment on the plan for the remaining development program. The Company plans to conduct two pivotal Phase 3 clinical trials and obtained agreement on the remaining Phase 1 clinical studies that the Company expects to conduct to support the New Drug Application (NDA) submission. The Company plans to conduct the Phase 3 trials in parallel with each other and is on track to initiate the first Phase 3 trial in the second quarter of 2026 and the second Phase 3 trial in the second half of 2026."

FDA event • New P3 trial • Chronic Cough • Idiopathic Pulmonary Fibrosis

The Effect of Nalbuphine Extended-release Tablets on Breathlessness in Patients With Idiopathic Pulmonary Fibrosis Experiencing Chronic Cough From the Phase 2b CORAL Trial (ATS 2026) - No abstract available

Clinical • P2b data • Chronic Cough • Cough • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

A Phase 2b Trial (CORAL) of Nalbuphine Extended-release Tablets in Patients With Idiopathic Pulmonary Fibrosis Experiencing Chronic Cough: Primary and Subgroup Analyses (ATS 2026) - No abstract available

Clinical • P2b data • Chronic Cough • Cough • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

Nalbuphine Extended Release Reduces Cough Bouts in Patients With Refractory Chronic Cough in the Phase 2a RIVER Trial (ATS 2026) - No abstract available

Clinical • P2a data • Chronic Cough • Cough • Respiratory Diseases

The Effect of Nalbuphine Extended Release on Cough Bouts in Patients With Idiopathic Pulmonary Fibrosis From a Phase 2b Randomized Clinical Trial (CORAL) (ATS 2026) - No abstract available

Clinical • P2b data • Cough • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

Pharmacokinetics and Safety Following Co-Administration of Nalbuphine Extended-Release With Pirfenidone or Nintedanib: A Phase 1 Drug-Drug Interaction Study (ATS 2026) - No abstract available

Clinical • Late-breaking abstract • P1 data • PK/PD data

Oral Nalbuphine in Idiopathic Pulmonary Fibrosis-Associated Cough: The CORAL Randomized Clinical Trial. (PubMed, JAMA) - P2 | "For patients with IPF-associated chronic cough, all 3 doses of nalbuphine ER reduced objective cough frequency and the 2 higher doses improved patient-reported cough frequency at 6 weeks. ClinicalTrials.gov Identifier: NCT05964335."

Clinical • Journal • Chronic Cough • Cough • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

NAL ER IPF Respiratory Function and Safety Study (clinicaltrials.gov) - P1 | N=10 | Recruiting | Sponsor: Trevi Therapeutics | Trial completion date: Oct 2025 ➔ Feb 2026 | Trial primary completion date: Sep 2025 ➔ Feb 2026

Trial completion date • Trial primary completion date • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

Trevi Therapeutics Outlines Key Development Milestones for Lead Drug Candidate (AD HOC NEWS) - "Trevi Therapeutics has provided investors with a definitive timeline for the advancement of Haduvio (oral nalbuphine ER), its lead therapeutic candidate. The company confirmed it will hold a critical End-of-Phase 2 (EOP2) meeting with the U.S. Food and Drug Administration (FDA) in the first quarter of 2026. Following this regulatory discussion, Trevi intends to initiate a Phase 3 clinical trial for chronic cough associated with idiopathic pulmonary fibrosis (IPF) in the first half of that same year....Concurrently, the company is preparing to start a Phase 2b study for refractory chronic cough (RCC), also slated for the first half of 2026."

FDA event • New P2b trial • New P3 trial • Chronic Cough • Idiopathic Pulmonary Fibrosis

Efficacy and safety of nalbuphine extended-release in refractory chronic cough: results from the phase 2a RIVER trial (BTS WM 2025) - P2 | "The most common (≥10%) TEAEs were constipation, somnolence, nausea, dizziness, headache, and fatigue. Download figure Open in new tab Download powerpoint Abstract P113 Figure 1 Relative Change from Baseline at Day 21 (108 mg BID) Conclusions The significant reduction in 24-h cough frequency supports further investigation of NAL ER for RCC."

Clinical • P2a data • Chronic Cough • Constipation • Cough • Gastroenterology • Gastrointestinal Disorder • Renal Cell Carcinoma • Respiratory Diseases • STAT2

…Recent Business Highlights: Chronic Cough in IPF (PRNewswire) - "The Company is preparing to request an End-of-Phase 2 meeting in the fourth quarter of 2025 and to initiate its Phase 3 program in the first half of 2026. The safety review committee for the Phase 1 respiratory function and safety study in patients with IPF, which is referred to as TIDAL, met to review data for the sentinel cohort of patients and concluded there were no safety signals and gave approval to complete enrollment. The study is expected to be completed in the fourth quarter of 2025 and available data will be included in the End-of-Phase 2 meeting package."

DSMB • FDA event • New P3 trial • Trial completion • Chronic Cough • Idiopathic Pulmonary Fibrosis

…Recent Business Highlights:…Refractory Chronic Cough (PRNewswire) - "Following the positive Phase 2a RIVER trial results earlier this year, the Company is planning to initiate a Phase 2b RCC study in the first half of 2026."

New P2b trial • Chronic Cough

Hydrogen bonding exacerbates viscoelasticity of amino acid- and betaine surfactant self-assemblies. (PubMed, J Colloid Interface Sci) - "The formation of wormlike micelles of sodium N-lauroyl l-serinate (NaLSer) and laurylamidopropyl betaine (LAPB) are quantified by the characteristic scattering of elongated objects in small-angle neutron scattering, and by the distinct shear-thinning and viscoelasticity measured through rheometry. In stark contrast, the absence of hydrogen bonding groups inhibits elongation, only able to form inviscid, spheroidal micelles for mixtures of sodium N-lauroyl l-alaninate (NaLAla) and lauryl betaine (LB). It is evident that hydrogen bonding stimulates uni-axial growth of micelles, enhancing viscosity and control over flow properties for applications in personal care, active delivery and rheological modification."

Journal

A RANDOMIZED, PLACEBO-CONTROLLED, PARALLEL-GROUP PHASE 2B TRIAL OF NALBUPHINE EXTENDED-RELEASE FOR CHRONIC COUGH IN PATIENTS WITH IDIOPATHIC PULMONARY FIBROSIS (CHEST 2025) - P2 | "In a population with IPF and CC, treatment with NAL ER significantly reduced objective cough frequency and improved outcomes directly reported by patients. CLINICAL IMPLICATIONS: As cough is a major contributor to impaired quality of life in patients with IPF, this study is important because it shows that effective reduction of cough frequency and severity by use of NAL ER significantly improved patients' quality of life."

Clinical • Late-breaking abstract • P2b data • Chronic Cough • Constipation • Cough • Gastroenterology • Gastrointestinal Disorder • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

PATIENT-REPORTED OUTCOMES FROM A PHASE 2A TRIAL OF EXTENDED-RELEASE NALBUPHINE FOR PATIENTS WITH REFRACTORY CHRONIC COUGH (CHEST 2025) - P2 | "NAL ER treatment improved PRO measures in patients with RCC, including patient perception of cough severity and cough frequency. CLINICAL IMPLICATIONS: No therapies have been approved in the United States for patients with RCC. NAL ER treatment demonstrated significant improvement in objective and PRO measures, warranting further development of NAL ER for patients with RCC."

Clinical • Late-breaking abstract • P2a data • Patient reported outcomes • Chronic Cough • Cough • Renal Cell Carcinoma • Respiratory Diseases

A Study of the Pharmacokinetic Interaction Between Pirfenidone, Nintedanib, and Nalbuphine Extended Release (NAL ER) in Healthy Participants (clinicaltrials.gov) - P1 | N=132 | Completed | Sponsor: Trevi Therapeutics | Recruiting ➔ Completed

Trial completion

Trevi Therapeutics, Inc…announced the acceptance of two abstracts for presentation at the CHEST 2025 Annual Meeting, to be held from October 19 to 22 in Chicago, Illinois. (Trevi Therapeutics) - "The key safety and efficacy results from the Phase 2b CORAL dose-ranging trial of nalbuphine ER for the treatment of chronic cough in patients with IPF was accepted for oral presentation. Additionally, patient-reported outcome results from the Phase 2a RIVER proof-of-concept trial of nalbuphine ER for the treatment of patients with RCC will be featured as a poster presentation."

P2a data • P2b data • Chronic Cough • Idiopathic Pulmonary Fibrosis

Late Breaking Abstract - Efficacy and safety of nalbuphine extended-release in refractory chronic cough: results from the phase 2a RIVER trial (ERS 2025) - P2 | "The significant reduction in 24-h cough frequency supports further investigation of NAL ER for RCC."

Clinical • Late-breaking abstract • P2a data • Chronic Cough • Constipation • Cough • Fatigue • Gastroenterology • Gastrointestinal Disorder • Renal Cell Carcinoma • Respiratory Diseases

Late Breaking Abstract - Responder analysis of nalbuphine extended-release in refractory chronic cough: results from the RIVER phase 2a trial (ERS 2025) - P2 | "These results support further investigation of NAL ER for the treatment of RCC."

Late-breaking abstract • P2a data • Chronic Cough • Cough • Renal Cell Carcinoma • Respiratory Diseases

Trevi Therapeutics Announces Two Posters from the Phase 2a RIVER Trial Data Will be Featured at the European Respiratory Society (ERS) Congress 2025 (PRNewswire)

P2a data • Chronic Cough

A Study of the Pharmacokinetic Interaction Between Pirfenidone, Nintedanib, and Nalbuphine Extended Release (NAL ER) in Healthy Participants (clinicaltrials.gov) - P1 | N=130 | Recruiting | Sponsor: Trevi Therapeutics | Not yet recruiting ➔ Recruiting

Enrollment open

Stability and physical compatibility of parenteral nalbuphine hydrochloride during continuous infusion in pediatrics. (PubMed, PLoS One) - "Nalbuphine hydrochloride in NS was found to be compatible with several drugs, but was incompatible with furosemide and amphotericin B. Nalbuphine hydrochloride can be administered in pediatric practice using a syringe pump for 24 h. However, drug-drug incompatibilities need to be considered when it is administered through a multiport manifold or Y-site connection."

Journal • Pediatrics

Pseudomonas aeruginosa in dental unit waterlines: an emerging threat of virulence genes in healthcare-associated infections. (PubMed, BMC Oral Health) - "These findings highlight that DUWLs act as reservoirs for P. aeruginosa strains harboring multiple virulence genes associated with biofilm formation. Targeted strategies are urgently needed to disrupt both bacterial growth and gene expression, which could help reduce antibiotic resistance and improve infection control in dental care."

Journal • Infectious Disease