A Study of the Pharmacokinetic Interaction Between Pirfenidone, Nintedanib, and Nalbuphine Extended Release (NAL ER) in Healthy Participants

NCT07015398 | Completed Phase 1 FDA Drug

• 1 other identifier: NAL00-105
• Study Type: interventional
• Target: 132
• Locations: 1 country
• Sites: 1

Brief Summary

The primary purpose of this study is to evaluate the effect of steady-state NAL ER on the pharmacokinetics (PK) of pirfenidone or nintedanib and the effect of steady-state pirfenidone or nintedanib on the PK of NAL ER in healthy participants.

Conditions

Healthy Participants

Outcome Measures

Primary Outcomes (8)

• Maximum Plasma Concentration (Cmax) of NAL ER, Pirfenidone, and Nintedanib

  Pre-dose and at multiple timepoints post-dose on Days 1 and 6 for Cohorts A1 and B1; on Days 1 and 8 for Cohort A2; on Days 1 and 7 for Cohort B2

• Time to Reach Maximum Observed Concentration (Tmax) of NAL ER, Pirfenidone, and Nintedanib

  Pre-dose and at multiple timepoints post-dose on Days 1 and 6 for Cohorts A1 and B1; on Days 1 and 8 for Cohort A2; on Days 1 and 7 for Cohort B2

• Area Under the Concentration-Time Curve From Time Zero to Time of Last Measurable Concentration (AUC0-Tlast) of NAL ER, Pirfenidone, and Nintedanib

  Pre-dose and at multiple timepoints post-dose on Days 1 and 6 for Cohorts A1 and B1; on Days 1 and 8 for Cohort A2; on Days 1 and 7 for Cohort B2

• Area Under the Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of NAL ER, Pirfenidone, and Nintedanib

  Pre-dose and at multiple timepoints post-dose on Days 1 and 6 for Cohorts A1 and B1; on Days 1 and 8 for Cohort A2; on Days 1 and 7 for Cohort B2

• Apparent Terminal Rate Constant (λz) of NAL ER, Pirfenidone, and Nintedanib

  Pre-dose and at multiple timepoints post-dose on Days 1 and 6 for Cohorts A1 and B1; on Days 1 and 8 for Cohort A2; on Days 1 and 7 for Cohort B2

• Apparent Terminal Half-Life (t1/2) of NAL ER, Pirfenidone, and Nintedanib

  Pre-dose and at multiple timepoints post-dose on Days 1 and 6 for Cohorts A1 and B1; on Days 1 and 8 for Cohort A2; on Days 1 and 7 for Cohort B2

• Apparent Clearance (CL/F) of NAL ER, Pirfenidone, and Nintedanib

  Pre-dose and at multiple timepoints post-dose on Days 1 and 6 for Cohorts A1 and B1; on Days 1 and 8 for Cohort A2; on Days 1 and 7 for Cohort B2

• Apparent Volume of Distribution (Vz/F) of NAL ER, Pirfenidone, and Nintedanib

  Pre-dose and at multiple timepoints post-dose on Days 1 and 6 for Cohorts A1 and B1; on Days 1 and 8 for Cohort A2; on Days 1 and 7 for Cohort B2

Secondary Outcomes (2)

• Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs)

  Up to Day 21

• Number of Participants With Clinically Significant Abnormalities in Vital Signs

  Up to Day 21

Study Arms (4)

Cohort A1 - NAL ER + Pirfenidone

EXPERIMENTAL

Participants will receive NAL ER followed by NAL ER co-administered with pirfenidone.

Drug: NAL ER; Drug: Pirfenidone

Cohort A2 - NAL ER + Nintedanib

EXPERIMENTAL

Participants will receive NAL ER followed by NAL ER co-administered with nintedanib.

Drug: NAL ER; Drug: Nintedanib

Cohort B1 - Pirfenidone + NAL ER

EXPERIMENTAL

Participants will receive pirfenidone followed by pirfenidone co-administered with NAL ER.

Drug: NAL ER; Drug: Pirfenidone

Cohort B2 - Nintedanib + NAL ER

EXPERIMENTAL

Participants will receive nintedanib followed by nintedanib co-administered with NAL ER.

Drug: NAL ER; Drug: Nintedanib

Interventions

NAL ER DRUG

Oral tablets

Also known as: Nalbuphine Extended Release

Cohort A1 - NAL ER + Pirfenidone; Cohort A2 - NAL ER + Nintedanib; Cohort B1 - Pirfenidone + NAL ER; Cohort B2 - Nintedanib + NAL ER

Pirfenidone DRUG

Oral tablets

Also known as: ESBRIET®

Cohort A1 - NAL ER + Pirfenidone; Cohort B1 - Pirfenidone + NAL ER

Nintedanib DRUG

Oral capsules

Also known as: OFEV®

Cohort A2 - NAL ER + Nintedanib; Cohort B2 - Nintedanib + NAL ER

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Body mass index (BMI) ≥ 18.0 and ≤ 30.0 kilogram per meter square (kg/m\^2) at Screening.
• Medically healthy with no clinically significant medical history, physical examination, laboratory profiles, vital signs or electrocardiograms (ECGs), as deemed by the principal investigator (PI) or designee.

You may not qualify if:

• Positive results for coronavirus infection (COVID-19).
• History or presence of alcohol or drug abuse.
• Positive urine drug or alcohol results.
• Smoker who has used nicotine containing products within the last 3 months.
• History or presence of hypersensitivity or idiosyncratic reaction to the study drugs or related compounds.
• Hemoglobin, absolute neutrophil count, or platelet levels outside of the reference range at Screening.
• History of prolonged QT syndrome or a QTc interval.
• Abnormal liver function at Screening or historical or concurrent liver disease.
• Positive results for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV).
• Abnormal Estimated glomerular filtration rate (eGFR).
• History of difficulty donating blood or donation of blood or plasma within 56 days of Screening.
• Participation in another clinical study within 30 days of the baseline visit.

Sponsors & Collaborators

• Trevi Therapeutics: lead

Study Sites (1)

Clinical Pharmacology of Miami

Miami, Florida, 33172, United States

Location

MeSH Terms

Interventions

pirfenidone; nintedanib

Study Officials

• Chief Development Officer

  Trevi Therapeutics

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 3, 2025
• First Posted: June 11, 2025
• Study Start: June 30, 2025
• Primary Completion: September 12, 2025
• Study Completion: September 26, 2025
• Last Updated: October 10, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)