Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
nalbuphine · 8 trials · 8 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.
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 | 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. |
| Placebo | PLACEBO_COMPARATOR | During the DB period, participants perceived a titration period of 2 weeks during which they received placebo to match the active titration period, followed by placebo, orally, BID, for 12 weeks. During the OLE period, participants were titrated over 2 weeks to NAL ER 162 mg, orally, BID, which they received for 38 weeks (including titration). |
| 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 |
| 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 |
|---|---|---|
| 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: * Individuals diagnosed with generalized nodular PN, covering 2 separate body parts, and 10 or more pruriginous nodules * Severe itch due to PN * Age 18 years and older at the time of consent, and a life expectancy of at least 18 months. * Individuals using antidepressants must ...