Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as Nalbuphine HCl solution, Nalbuphine, Nalbuphine HCL ER, NAL ER, NAL, Nalbuphine ER, Nalbuphine ER Tablets
Haduvio (nalbuphine ER) · 15 trials · 10 indications
The NRS is a patient related outcome (PRO) instrument, designed to quantify the intensity of worst itching experienced during a 24-hour period, and can be applied and validated either with reference to the average itch or to the absolute worst itch (WI-NRS) over that 24-hour period. WI-NRS is a set of boxes, one for each number, from 0 (no itching) to 10 (worst possible itching). Higher scores indicate worst itching experience. Responder was defined as a participant with a ≥4-point decrease in the 7-day average WI-NRS from baseline to Week 14.
Incidence of adverse events is calculated based on events observed on or after the date of first dose, where incidence is defined as the number of subjects who reported one or more events of a particular adverse event divided by the number of subjects who received at least one dose of investigational product. Overall incidence is the proportion of subjects who had one or more adverse events of any type and nature pertains to the incidence of individual events coded by MedDRA nomenclature. An additional consideration was to evaluate incidence of adverse events by dose achieved but this was not done as subjects achieved a maximum dose during the study that varied and, per protocol, dosing could be modified per the investigator, during the course of this extension to TR03. In addition, TR03EXT involved a dose titration whereas events could have been reported well before a subject achieved some partciular dose level. Consequently, such a presentation would have been impossible to discern.
The number of subjects who reported at least a 30% reduction from baseline to Week 10, expressed as a percentage of subjects in the particular arm/group who were evaluated,
The number of participants reporting at least one TEAE of a particular body system and preferred term are reported (incidence)
The evaluation period was defined as the average itch score over weeks 7 and 8 following initiation of treatment. A negative change form baseline (Evaluation Period - Baseline) signified inmprovement.
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.
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 clinical chemistry, hematology, coagulation, and urinalysis. Clinical significance was determined by the investigator.
Vital signs measurements included diastolic and systolic blood pressure, heart rate, respiratory rate, and body temperature. Clinical significance was determined by the investigator.
Physical examination included examination of at least the following components: head, eyes, ears, nose, throat (HEENT), neck, lungs, abdomen, skin, cardiovascular and musculoskeletal evaluation, and general neurological examination. Clinical significance was determined by the investigator.
ECG data included the measurement of heart rate and aggregate PR interval, QRS duration, QT interval, QTcB interval, and QTcF interval.
Oxygen saturation was measured via pulse oximetry. Pulse oximetry measurements were to be collected within 10 min before or after the specified time point. Clinical significance was determined by the investigator.
Only Part A of thie study was conducted because of closure the clinical research unit (CRU) before Part B could be initiated. Summary statistics are provided for C-max
Steady state PK of nalbuphine HCl ER tablets following escalating repeated oral doses in ESRD patients receiving HD therapy relative to healthy subjects
Extraction by dialysis was assessed by measuring nalbuphine concentrations in plasma during dialysis obtained from arterial (pre-dialyzer) and venous access ports (post-dialyzer) and by measuring the amount removed in the dialysate during dialysis in the dialysate as a function of dose.
| 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 12 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 12 weeks. |
| NAL ER | EXPERIMENTAL | During the double-blind (DB) period, participants were titrated over 2 weeks to NAL ER 162 mg, orally, twice daily (BID), followed by 162 mg, orally, BID, for 12 weeks. During the open label extension (OLE) period, participants perceived a titration period of 2 weeks, and continued to receive NAL ER 162 mg, orally, BID, for 38 weeks in total. |
| nalbuphine HCl ER | EXPERIMENTAL | nalbuphine HCl ER |
| nalbuphine HCl ER 90mg | EXPERIMENTAL | nalbuphine HCl ER tablets 90 mg BID |
| nalbuphine HCl ER 180 mg | EXPERIMENTAL | nalbuphine HCl ER tablets 180 mg BID |
| Sugar pill | PLACEBO_COMPARATOR | Placebo tablets BID |
| nalbuphine HCl ER 60mg | EXPERIMENTAL | nalbuphine HCl ER tablets 60 mg BID |
| nalbuphine HCl ER 120mg | EXPERIMENTAL | nalbuphine HCl ER tablets 120 mg BID |
| 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. |
| Part 1 Single Ascending Dose | EXPERIMENTAL | Participants with mild (group 1), moderate (group 2) and severe (group 3) hepatic impairment received single dose ranging from 27 mg up to 162 mg of NAL ER tablet under fasting conditions. There was a washout period of at least 7 days between the drug administration between each dose level. Participants with no hepatic impairment (group 4) received a single dose of NAL ER of up to 162 mg under fasting conditions. |
| 90 mg nalbuphine HCl solution | EXPERIMENTAL | 90 mg nalbuphine HCl solution 9 mL × 10 mg/mL hydromorphone HCl + 141 mL flavored beverage |
| 120 mg nalbuphine HCl solution | EXPERIMENTAL | 120 mg nalbuphine HCl solution 12 mL × 10 mg/mL hydromorphone HCl + 138 mL flavored beverage |
| 150 mg nalbuphine HCl solution | EXPERIMENTAL | 150 mg nalbuphine HCl solution 15 mL × 10 mg/mL hydromorphone HCl + 135 mL flavored beverage |
| 180 mg nalbuphine HCl solution | EXPERIMENTAL | 180 mg nalbuphine HCl solution 18 mL × 10 mg/mL hydromorphone HCl + 132 mL flavored beverage |
| 270 mg nalbuphine HCl solution | EXPERIMENTAL | 270 mg nalbuphine HCl solution 27 mL × 10 mg/mL hydromorphone HCl + 123 mL flavored beverage |
| Up to 405 mg nalbuphine HCl solution | EXPERIMENTAL | Up to 405 mg nalbuphine HCl solution Up to 40.5 mL × 10 mg/mL hydromorphone HCl + at least 109.5 mL flavored beverage |
| Up to 540 mg nalbuphine HCl solution | EXPERIMENTAL | Up to 540 mg nalbuphine HCl solution Up to 54 mL × 10 mg/mL hydromorphone HCl + at least 96 mL flavored beverage |
| Cohort 1 - Groups 1-3 | EXPERIMENTAL | HD patients dosing up to 180mg BID |
| Cohort 1 - Group 4 | EXPERIMENTAL | HD patients dosing up to 240mg BID |
| Cohort 2 | EXPERIMENTAL | Healthy patients dosing up to 180mg BID |
| Name | Type | Description |
|---|---|---|
| NAL ER | DRUG | Oral tablets |
| Placebo | DRUG | Oral tablets |
| Nalbuphine ER Tablets | DRUG | Active Nalbuphine ER Tablets |
| Placebo Tablets | DRUG | Placebo matching NAL ER with no active substance |
| nalbuphine HCl ER | DRUG | nalbuphine HCl ER BID for up to 50 weeks |
| nalbuphine HCl ER tablets 90 mg BID | DRUG | nalbuphine HCl ER tablets 90 mg BID administered for 8 weeks |
| nalbuphine HCl ER tablets 180 mg BID | DRUG | nalbuphine HCl ER tablets 180 mg BID administered for 8 weeks |
| Placebo tablets BID | DRUG | Placebo tablets BID administered for 10 weeks |
| nalbuphine HCl ER tablets 60 mg BID | DRUG | nalbuphine HCl ER tablets 60 mg BID administered for 6 weeks |
| nalbuphine HCl ER tablets 120mg BID | DRUG | nalbuphine HCl ER tablets 120mg BID administered for 6 weeks |
| Nalbuphine ER | DRUG | Oral tablet |
| Nalbuphine HCl solution | DRUG | nalbuphine solution administered at various strengths |
| Placebo solution | DRUG | Placebo |
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...
Top 15 of 17 competitors
Haduvio is an extended-release oral formulation of nalbuphine being studied for chronic cough associated with idiopathic pulmonary fibrosis and for refractory chronic cough. It is also being evaluated in hepatic impairment and has been studied in uremic pruritus and prurigo nodularis. It is an investigational product and has not been approved for these uses.
Haduvio is being developed by Trevi Therapeutics, Inc., which trades on the Nasdaq under the ticker TRVI. Trevi is the sponsor of the clinical program evaluating nalbuphine extended-release tablets across cough and pruritus indications.
Haduvio is in clinical development, with Phase 3 trials currently recruiting in idiopathic pulmonary fibrosis-related chronic cough and a Phase 2 trial recruiting in refractory chronic cough. A Phase 1 respiratory function and safety study in idiopathic pulmonary fibrosis has been completed. The program overall is listed at Phase 1, and the product is investigational.
Recruiting studies include NCT07671911 and NCT07868419, both Phase 3 trials of nalbuphine extended-release tablets in idiopathic pulmonary fibrosis-related chronic cough, and NCT07671924, a Phase 2 trial in refractory chronic cough. The completed Phase 1 NAL ER IPF respiratory function and safety study is NCT07036029.
Yes. Haduvio is the brand name for nalbuphine extended-release, also written as nalbuphine ER, NAL ER, or nalbuphine HCl ER. Other names used for the same asset include nalbuphine, nalbuphine HCl solution, and nalbuphine HCl ER tablets at 60 mg and 90 mg twice daily.
Across the Haduvio clinical program, 723 participants are enrolled in five trials. Three of those trials are completed and two are active and recruiting. The studies are uncontrolled, without randomization or double blinding, and enrollment includes adults with idiopathic pulmonary fibrosis or refractory chronic cough.