Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as NAL ER
NAL · 8 trials · 3 indications
Relative change in 24-hour (combined daytime and nighttime) cough frequency (coughs per hour) from baseline was assessed. Assessment was done using objective digital cough monitoring. Baseline was defined as the last non-missing assessment, prior to the first dose of study drug.
An AE was defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A TEAE was defined as any AE that occurs after the first dose of study drug. TEAEs included both serious and non-serious TEAEs.
The clinical laboratory parameters included the urinalysis, hematology, serum chemistry, coagulation and liver function parameters. Clinical significance was determined by the investigator.
Vital signs measurements included blood pressure, heart rate, and respiration rate, body temperature, pulse oximetry, and weight. Clinical significance was determined by the investigator.
Physical examination included examination of the following body systems: general appearance, eyes, ears, nose, throat, head and neck, chest and lungs, cardiovascular, abdomen, musculoskeletal, lymphatic, dermatological, neurological, and extremities. Clinical significance was determined by the investigator.
Changes in ECG data such as heart rate, rhythm, and other clinically significant abnormalities (left ventricular hypertrophy, pathological Q-waves) were measured. Clinical significance was determined by the investigator.
Spirometry was used to assess FVC. It was used to assess pulmonary breathing mechanics.
The SOWS is a self-administered scale for grading opioid withdrawal symptoms and was collected via the study issued e-diary. It consisted of 16 symptoms related to how the participant felt. Each symptom was scored between 0 to 4. The total score ranges between 0 to 64, higher score indicates more severe symptoms.
Daytime cough was defined as cough that occurs between the time that the participant is a wake in the 24 hours after the digital cough monitor was applied for use. Assessment was done using objective digital cough monitoring. Baseline was defined as the last available assessment prior to the first Treatment Period 1 IP intake.
Daytime cough was defined as cough that occurs between the time that the participant is a wake in the 24 hours after the digital cough monitor was applied for use. Assessment was done using objective digital cough monitoring. Percent change in daytime cough frequency (coughs per hour) from baseline was assessed. Baseline was defined as the last available assessment prior to the first Treatment Period 1 IP intake.
| Arm | Type | Description |
|---|---|---|
| NAL ER 54 mg | EXPERIMENTAL | Participants will undergo a 2-week blinded titration period followed by a fixed dose treatment period receiving NAL ER 54 milligrams (mg) twice daily (BID) for 52 weeks. |
| Placebo | PLACEBO_COMPARATOR | Participants will undergo a 2-week blinded titration period followed by a fixed dose treatment period receiving a matching placebo BID for 52 weeks. |
| NAL ER 54 mg BID | EXPERIMENTAL | Participants will receive NAL ER during the titration period, with dose titration starting at 27 milligrams (mg) once daily (QD) and increasing up to 54 mg twice daily (BID) from Day 1 to Day 14. Participants will receive NAL ER 54 mg BID during the fixed-dose treatment period from Day 15 to Day 42. |
| NAL ER 27 mg BID | EXPERIMENTAL | Participants will receive NAL ER during the titration period, starting at 27 mg QD to 27 mg BID from Day 1 to Day 14. Participants will receive NAL ER 27 mg BID during the fixed-dose treatment period from Day 15 to Day 42. |
| NAL ER 27 mg QD | EXPERIMENTAL | Participants will receive NAL ER 27 mg QD during the titration period from Day 1 to Day 14. Participants will continue to receive NAL ER 27 mg QD during the fixed-dose treatment period from Day 15 to Day 42. |
| NAL ER 27 mg | EXPERIMENTAL | Participants were titrated over 2 weeks to NAL ER 27 mg BID, then maintained at the fixed dose for 4 weeks (total 6 weeks of treatment). |
| NAL ER 108 mg | EXPERIMENTAL | Participants were titrated over 2 weeks to NAL ER 108 mg BID, then maintained at the fixed dose for 4 weeks (total 6 weeks of treatment). |
| First NAL ER, then Placebo | EXPERIMENTAL | Participants received NAL ER at escalating doses (27 mg QD to BID, 54 mg BID, and 108 mg BID) in Treatment Period 1, followed by placebo matched to NAL ER in Treatment Period 2. |
| First Placebo then NAL ER | EXPERIMENTAL | Participants received placebo matched to NAL ER in Treatment Period 1, followed by NAL ER at escalating doses (27 mg QD to BID, 54 mg BID, and 108 mg BID) in Treatment Period 2. |
| NAL ER then placebo | EXPERIMENTAL | Participants received NAL ER in treatment period 1 at dose 27 mg once daily (QD) to 54 mg twice daily (BID) over a 5-day period and then maintained at 54 mg BID for 4 days. Dose was increased to 108 mg BID for 1 week then to 162 mg BID for 6 days, followed by placebo matching NAL ER for 3 weeks in treatment period 2. Both the treatment periods were separated by 2 weeks of washout period. |
| Placebo then NAL ER | EXPERIMENTAL | Participants received placebo matching NAL ER for 3 weeks in treatment period 1 followed by NAL ER in treatment period 2 at dose 27 mg QD to 54 mg BID over a 5-day period and then maintained at 54 mg BID for 4 days. Dose was increased to 108 mg BID for 1 week then to 162 mg BID for 6 days. Both the treatment periods were separated by 2 weeks of washout period. |
| Cohort 1: NAL ER Dose A | EXPERIMENTAL | Participants will receive NAL ER Dose A on Day 1 in the fasted state, followed by dosing on Day 5 in the fed state in the first sequence, and vice versa in the second sequence, with a 3-day washout maintained between sequences. |
| Cohort 2: NAL ER Dose B | EXPERIMENTAL | Participants will receive NAL ER Dose B on Day 1 in the fasted state, followed by dosing on Day 5 in the fed state in the first sequence, and vice versa in the second sequence, with a 3-day washout maintained between sequences. |
| NAL ER | EXPERIMENTAL | Participants will receive 2 doses of placebo (placebo matching NAL ER) over 2 days followed by increasing doses of NAL ER tablets twice daily (BID) over 6 days. |
| Cohort A1 - NAL ER + Pirfenidone | EXPERIMENTAL | Participants will receive NAL ER followed by NAL ER co-administered with pirfenidone. |
| Cohort A2 - NAL ER + Nintedanib | EXPERIMENTAL | Participants will receive NAL ER followed by NAL ER co-administered with nintedanib. |
| Cohort B1 - Pirfenidone + NAL ER | EXPERIMENTAL | Participants will receive pirfenidone followed by pirfenidone co-administered with NAL ER. |
| Cohort B2 - Nintedanib + NAL ER | EXPERIMENTAL | Participants will receive nintedanib followed by nintedanib co-administered with NAL ER. |
| Name | Type | Description |
|---|---|---|
| NAL ER | DRUG | Oral tablets |
| Placebo | DRUG | Oral tablets |
| Pirfenidone | DRUG | Oral tablets |
| Nintedanib | DRUG | Oral capsules |
Inclusion Criteria: * Diagnosis of IPF as determined by the Investigator based on American Thoracic Society (ATS)/European Respiratory Society (ERS)/Japanese Respiratory Society (JRS)/Latin American Thoracic Society (ALAT) clinical practice guidelines. * Chronic cough for ≥8 weeks prior to Screenin...
| Company | Ticker | Trials | Lead Phase | Drugs |
|---|---|---|---|---|
| Bristol-Myers Squibb Company | BMY | 2 | PHASE3 | BMS-986278 |
| United Therapeutics Corporation | UTHR | 2 | PHASE3 | Treprostinil |
| AbbVie, Inc. | ABBV | 2 | PHASE2 | ABBV-142 |
| PureTech Health PLC Sponsored ADR | PRTC | 2 | PHASE3 | Deupirfenidone, Pirfenidone |
| Syndax Pharmaceuticals Inc | SNDX | 1 | PHASE2 | Axatilimab |
| Contineum Therapeutics, Inc. Class A | CTNM | 1 | PHASE2 | PIPE-791 Dose A, PIPE-791 Dose B |
| Rein Therapeutics, Inc | RNTX | 1 | PHASE2 | LTI-03 |
| Sunshine Biopharma Incorporated | SBFM | 2 | PHASE3 | HEC585, Pirfenidone |
| Cumberland Pharmaceuticals Inc. | CPIX | 1 | PHASE2 | Ifetroban |
| Avalyn Pharma Inc | AVLN | 3 | PHASE2 | AP01 |
NAL, also known as NAL ER, is an investigational extended-release formulation of nalbuphine being studied for the treatment of chronic cough associated with idiopathic pulmonary fibrosis (IPF) and refractory chronic cough. It is a small molecule being developed by Trevi Therapeutics, Inc. (TRVI) and is currently in clinical trials.
NAL targets the kappa opioid receptor (KOR) and mu opioid receptor (muOR). By acting on these receptors, it is being investigated for its potential to reduce cough in patients with conditions such as idiopathic pulmonary fibrosis and refractory chronic cough.
NAL is being developed by Trevi Therapeutics, Inc., a biopharmaceutical company traded under the ticker symbol TRVI. The company is conducting clinical trials to evaluate NAL ER for the treatment of chronic cough in various patient populations.
NAL is in Phase 1 clinical development. However, it is also being studied in later-phase trials: a Phase 2 trial for refractory chronic cough and a Phase 3 trial for IPF-related chronic cough are currently recruiting participants. NAL is investigational and not yet approved.
NAL is being evaluated in several clinical trials, including NCT07671924 (Phase 2 for refractory chronic cough), NCT07671911 (Phase 3 for IPF-related chronic cough), NCT07487740 (Phase 1 food effect study in healthy participants), and NCT07036029 (Phase 1 respiratory function study in IPF). These trials are conducted in the US, Canada, and the UK.
Yes, NAL is also known as NAL ER, which stands for nalbuphine extended-release. The terms are used interchangeably in clinical trials and development programs to refer to the same investigational drug product.