Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 2018-001219-53 | EudraCT Number |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
To investigate the anti-pruritic efficacy and safety of Nalbuphine Extended Release (ER) (NAL ER) tablets in Prurigo Nodularis. Participants were randomized to NAL ER (or matching placebo) with the primary endpoint evaluation at Week 14. During the open label extension, participants who received NAL ER were continued on NAL ER and participants who received placebo would then shift to NALER.
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Nalbuphine ER Tablets | Drug | Active Nalbuphine ER Tablets |
|
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants With ≥ 4- Point Decrease in 7-day Average Worst Itch - Numerical Rating Scale (WI-NRS) up to Week 14 | 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. | Baseline up to Week 14 |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Itch-related Quality of Life (ItchyQoL) Total Score at Week 14 | The ItchyQoL consists of 22 pruritus-specific items measuring how pruritus affects participant's QoL in the area of symptoms related to the itch condition (6 questions), functional limitations (7 questions), and emotions (9 questions). The participant scored each question never = 1, rarely = 2, sometimes = 3, often = 4, all the time = 5. The ItchyQoL total score were obtained as the sum of the 22 items ranging from 22 to 110, with higher score indicating worsening of pruritus. A negative change from baseline indicated improvement in the pruritus-related difficulties. |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Pruritus due to localized PN (only one body part affected), or less than 10 nodules
Active, uncontrolled, pruritic dermatoses in need of treatment (such as atopic dermatitis or bullous pemphigoid for example).
History of a major psychiatric disorder such as bipolar disorder or schizophrenia. History of active substance abuse in the last 3 years.
Known intolerance [gastrointestinal (GI), central nervous system (CNS) symptoms] or hypersensitivity/drug allergy to opioids.
Use of certain concomitant medications and treatments within a period prior to the study, or requirement for these medications during the study:
Myocardial infarction or acute coronary syndrome within the previous 3 months, as reported by the participant.
Individuals with prolonged QT interval corrected for heart rate using Fridericia's formula (QTcF).
Note: Other Inclusion/Exclusion criteria may apply.
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Chief Development Officer | Trevi Therapeutics | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Study Site 151 | Phoenix | Arizona | 85006 | United States | ||
| Study Site 121 |
Not provided
Not provided
Not provided
Not provided
Not provided
A total of 608 participants were screened, out of which 353 participants were randomized, and 344 participants were treated with NAL ER and/or placebo.
Participants were enrolled at 70 sites in Germany, Poland, Austria, France and the United States from 07 August 2018 to 24 February 2023.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | NAL ER | 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. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jul 21, 2021 | Apr 23, 2025 |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Placebo Tablets | Drug | Placebo matching NAL ER with no active substance |
|
| Baseline, Week 14 |
| Change From Baseline in Prurigo Activity Score (PAS) Assessed by the Percentage of Participants With 1-Category Improvement in the Percentage of Pruriginous Lesions With Excoriations/Crusts (Item 5a) at Week 14 | PAS consists of 5 quantitative/qualitative measurements related to examination of skin: Type; number;distribution;quantitative number of lesions in a body part;activity. Prurigo lesion activity is recorded as a stage (0 to 4), based on percentage of overall lesions with relevant characteristic. Three types of PAS responders defined one for each of the following items: Pruriginous lesions with excoriations/crusts (item 5a);Healed lesions (item 5b);Number of lesions (item 2). Pruriginous lesions with excoriations/crusts (item 5a) was recorded from 0 to 4;where 0 = 0-25%1 = 26-50%,2 = 51-75%,3 = 76-90%,4 = 91-100%. Higher score=a greater number of pruriginous lesions with excoriations/crusts. A responder was defined as a participant who has at least 1-category improvement in the relevant item from baseline to Week 14. Baseline is defined as the last non-missing evaluation (including repeated and unscheduled assessments) taken prior to or on the date of first dose of study medication. | Baseline, Week 14 |
| Change From Baseline in Patient-Reported Outcomes Measurement Information System (PROMIS) Sleep Disturbance Short Form 8a at Week 14 | PROMIS Sleep Disturbance Short Form 8a questionnaire is a tool for assessing sleep. It has 8 questions which measures sleep in the past 7 days.There is 1 broad sleep quality question with options:"very poor","poor","fair","good",and "very good".Remaining 7 questions are answered with:"not at all","a little bit","somewhat","quite a bit",and "very much".Lowest possible raw score=8; highest possible raw score=40. The T-score rescales raw score into a standardized score with a mean of 50 and an standard deviation of 10 derived from general population.Lowest possible T-score=28.9;highest possible T-score=76.6.Higher T-score shows more of the concept measured,higher the T-Score worse the sleep disturbance.Scores <55=normal limits, 55-60=mild, 61-70=moderate,and >70=severe sleep disturbance.Baseline=last non-missing evaluation (including repeated and unscheduled assessments) taken prior to or on the date of first dose of study medication.Negative change from baseline indicated better sleep. | Baseline, Week 14 |
| Change From Baseline in 7-Day Average WI-NRS to Week 14 | The NRS is a 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. Baseline WI-NRS value was calculated as the arithmetic mean of the WI-NRS values (minimum of 5 required) taken for eligibility review by site at the time of randomization. A negative change from baseline indicates improvement in symptoms. | Baseline, Week 14 |
| Change From Baseline in PAS Assessed by the Percentage of Participants With 1-Category Improvement in the Percentage of Healed Lesions (Item 5b) at Week 14 | PAS consists of 5 quantitative/qualitative measurements related to skin-Type; number; distribution; quantitative number of lesions in body part; activity. Prurigo lesion activity is recorded as stage (0 to 4), based on percentage of overall lesions with relevant characteristic. Three types of PAS responders are defined: Pruriginous lesions with excoriations/crusts (item 5a); Healed lesions (item 5b); Number of lesions (item 2). Prurigo lesions (item 5b), where 0 = 100%,1 = 75-99%,2 = 50-74%,3 = 25-49%,4 = 0-24% healed pruriginous lesions. Lower score=more number of healed pruriginous lesions. A responder was defined as a participant who has at least 1-category improvement in the relevant item from baseline to Week 14. Baseline was defined as the last non-missing evaluation (including repeated and unscheduled assessments) taken prior to or on the date of first dose of treatment. A negative change from baseline would indicate higher number of healed lesions. | Baseline, Week 14 |
| Change From Baseline in PAS Assessed by the Percentage of Participants With 1-Category Improvement in the Percentage of Lesions (Item 2) at Week 14 | PAS consists of 5 quantitative/qualitative measurements of skin- Type; number; distribution; quantitative number of lesions in body part; activity. Prurigo lesion activity is recorded as stage (0 to 4) based on percentage of overall lesions with relevant characteristic. Three types of PAS responders are defined: Pruriginous lesions with excoriations/crusts (item 5a); Healed lesions (item 5b); Number of lesions (item 2). Prurigo lesion activity is recorded as a stage (0 to 4), based on the percentage of overall lesions with the relevant characteristic. A lower score indicates less number of pruriginous lesions. A responder was defined as a participant who has at least 1-category improvement in the relevant item from baseline to Week 14. Baseline was defined as the last non-missing evaluation (including repeated and unscheduled assessments) taken prior to or on the date of first dose of study medication. A negative change from baseline would indicate lower number of lesions. | Baseline, Week 14 |
| Change From Baseline in Investigator Global Assessment-Prurigo Nodularis (IGA-PN) Assessed by the Percentage of Participants With 1-Category Improvement in Activity at Week 14 | The IGA-PN collects an investigator global assessment of status of PN skin lesions. The IGA-PN uses a 5-category scale (scoring 0 to 4) to describe the status of 2 aspects of disease: The Activity (amount of excoriation and crusting associated with the prurigo lesions), and the Stage (the quantitative presence and proportion of flattening of the lesions). The excoriation/crusting activity on the surface (PN-Activity) where it considers number of PN lesion with excoriations and crusts on the top, 0=clear (No nodules), 1 =small number, 2=minority of nodules, 3=most nodules, 4=severe (vast majority of nodules). A higher number indicates severe status of PN skin lesions. An IGA-PN responder for activity was defined as participants who has at a least 1-category improvement in the respective score from baseline to Week 14. Baseline was defined as the last non-missing evaluation (including repeated and unscheduled assessments) taken prior to or on the date of first dose of study medication. | Baseline, Week 14 |
| Change From Baseline in IGA-PN Assessed by the Percentage of Participants With 1-Category Improvement in Stage at Week 14 | The IGA-PN collects an investigator global assessment of status of PN skin lesions. The IGA-PN uses a 5-category scale(scoring 0 to 4) to describe 2 aspects of disease. The Activity(amount of excoriation and crusting of prurigo lesions) and the Stage(the quantitative presence and proportion of flattening of lesions),where 0=clear(No nodules),1=Rare, flattened lesions, with no more than single dome-shaped palpable nodules(1-5 nodules), 2=Few,mostly flattened lesions, with small number of dome-shaped palpable nodules(6-19 nodules,3=Many lesions, partially flattened and dome-shaped palpable nodules (20-100 nodules),4=Abundant lesions, majority are dome-shaped palpable nodules (over 100 nodules).Higher number= presence of abundant lesions.Responder as defined as participants who has at a least 1-category improvement from baseline to Week 14.Baseline was defined as the last non-missing evaluation(repeated and unscheduled assessments)taken prior to or on the date of first dose of treatment. | Baseline, Week 14 |
| Percentage of Participants Having a Patient Benefit Index, Pruritus Version (PBI-P) Score of ≥1 at Week 14 | PBI-P is an instrument that measures participant-defined treatment objectives and benefits acquired during the course of treatment.During and after therapy, the participant completes a matched "on-treatment" Treatment Benefits questionnaire and rates the extent to which the treatment objectives have been achieved.It consists of 27 multiple choice questions that can be answered "not at all","somewhat","moderately","quite","very".PBI-P global score is computed according to the score obtained for patient needs questionnaire (PNQ) and patient benefit questionnaire (PBQ).Score may only be computed if the participant has provided valid data on importance (PNQ) and benefit (PBQ) for at least 75% of the respective treatment goals,i.e., for at least 21 of the 27 items. Total score ranges from 0-135. Higher scores=more benefit received from the study to the participant.Responses "does/did not apply","question answered" are considered valid values when counting number of non-missing responses. | At Week 14 |
| Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinued From Study Drug Due to TEAEs in DB Period | An AE is any untoward medical occurrence in a participant who administered a pharmaceutical product, and which does not necessarily have to have a causal relationship with the study drug. 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 serious adverse event (SAE) is any untoward medical occurrence that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. DB period TEAEs are defined as AEs that either start or worsen in severity on or after the first DB dose and prior to the first extension titration dose of study medication in the OLE period. TEAEs included both serious & non-serious TEAEs. | Baseline up to Week 14 |
| Number of Participants Who Experienced TEAEs, Serious TEAEs, and Discontinued From Study Drug Due to TEAEs in OLE Period | An AE is 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 study drug. 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 serious adverse event (SAE) was any untoward medical occurrence that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. OLE period TEAEs are defined as AEs that either start or worsen in severity on or after the first extension titration dose of study medication. TEAEs included both serious & non-serious TEAEs. | From Week 14 up to Week 56 |
| Fremont |
| California |
| 94538 |
| United States |
| Study Site 157 | Laguna Niguel | California | 92677 | United States |
| Study Site 141 | North Hollywood | California | 91606 | United States |
| Study Site 130 | San Francisco | California | 94115 | United States |
| Study Site 128 | Washington D.C. | District of Columbia | 20037 | United States |
| Study Site 138 | Boca Raton | Florida | 33433 | United States |
| Study Site 158 | Orlando | Florida | 32819 | United States |
| Study Site 108 | South Miami | Florida | 33143 | United States |
| Study Site 142 | Tampa | Florida | 33615 | United States |
| Study Site 102 | Rockville | Maryland | 20850 | United States |
| Study Site 136 | Boston | Massachusetts | 02114 | United States |
| Study Site 153 | Brighton | Massachusetts | 02135 | United States |
| Study Site 143 | Ann Arbor | Michigan | 48103 | United States |
| Study Site 139 | Troy | Michigan | 48084 | United States |
| Study Site 118 | Saint Joseph | Missouri | 64506 | United States |
| Study Site 144 | Henderson | Nevada | 89052 | United States |
| Study Site 146 | Las Vegas | Nevada | 89119 | United States |
| Study Site 109 | Portsmouth | New Hampshire | 03801 | United States |
| Study Site 159 | Hackensack | New Jersey | 07601 | United States |
| Study Site 134 | Stony Brook | New York | 11794 | United States |
| Study Site 101 | Wilmington | North Carolina | 28411 | United States |
| Study Site 122 | Cincinnati | Ohio | 45219 | United States |
| Study Site 120 | Cleveland | Ohio | 44106 | United States |
| Study Site 132 | Hershey | Pennsylvania | 17033 | United States |
| Study Site 106 | Philadelphia | Pennsylvania | 19103 | United States |
| Study Site 131 | Johnston | Rhode Island | 02919 | United States |
| Study Site 147 | Charleston | South Carolina | 29407 | United States |
| Study Site 107 | Charleston | South Carolina | 29425-8908 | United States |
| Study Site 140 | Chattanooga | Tennessee | 37421 | United States |
| Study Site 145 | Knoxville | Tennessee | 37917 | United States |
| Study Site 137 | Austin | Texas | 78705 | United States |
| Study Site 103 | Webster | Texas | 77598 | United States |
| Study Site 150 | West Jordan | Utah | 84088 | United States |
| Study Site 135 | Spokane | Washington | 99202 | United States |
| Study Site 148 | Morgantown | West Virginia | 26505 | United States |
| Study Site 401 | Graz | 8036 | Austria |
| Study Site 402 | Linz | 4020 | Austria |
| Study Site 501 | Brest | 29609 | France |
| Study Site 502 | Paris | 75010 | France |
| Study Site 204 | Frankfurt am Main | Hesse | 60590 | Germany |
| Study Site 202 | Münster | North Rhine-Westphal | 48149 | Germany |
| Study Site 201 | Mainz | Rhineland-Palatinate | 55131 | Germany |
| Study Site 213 | Dresden | Saxony | 01307 | Germany |
| Study Site 205 | Bad Bentheim | 48455 | Germany |
| Study Site 216 | Berlin | 10117 | Germany |
| Study Site 209 | Berlin | 10247 | Germany |
| Study Site 208 | Berlin | 10789 | Germany |
| Study Site 219 | Cologne | 50937 | Germany |
| Study Site 221 | Düsseldorf | 40225 | Germany |
| Study Site 215 | Hamburg | 20246 | Germany |
| Study Site 222 | Hamburg | 22391 | Germany |
| Study Site 212 | Heidelberg | 69115 | Germany |
| Study Site 214 | Kiel | 24105 | Germany |
| Study Site 220 | München | 80802 | Germany |
| Study Site 206 | Stuttgart | 70178 | Germany |
| Study Site 304 | Bialystok | 15-453 | Poland |
| Study Site 306 | Katowice | 40-648 | Poland |
| Study Site 308 | Krakow | 31-302 | Poland |
| Study Site 316 | Krakow | 31-559 | Poland |
| Study Site 309 | Lodz | 90-265 | Poland |
| Study Site 314 | Lublin | 20-406 | Poland |
| Study Site 305 | Ostrowiec Świętokrzyski | 27-400 | Poland |
| Study Site 313 | Poznan | 60-529 | Poland |
| Study Site 315 | Poznan | 60-848 | Poland |
| Study Site 303 | Rzeszów | 35055 | Poland |
| Study Site 310 | Warsaw | 01-142 | Poland |
| Study Site 301 | Warsaw | 01-817 | Poland |
| Study Site 312 | Warsaw | 02-962 | Poland |
| Study Site 302 | Wroclaw | 50566 | Poland |
| FG001 |
| Placebo |
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). |
| Modified Intent-to-treat (mITT) Analysis Set | The mITT population included all randomized participants who received at least a single dose of investigational product (IP). |
|
| Participants Who Entered the OLE Period |
|
| COMPLETED |
|
| NOT COMPLETED |
|
|
The mITT population included all randomized participants who received at least a single dose of IP.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | NAL ER | During the DB period, participants were titrated over 2 weeks to NAL ER 162 mg, orally, BID, followed by 162 mg, orally, BID, for 12 weeks. During the 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. |
| BG001 | Placebo | 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). |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Worst Itch - Numerical Rating Scale (WI-NRS) Score | NRS is a patient related outcome (PRO) instrument to quantify the intensity of worst itching experienced for 24-hour period and can be applied and validated either with reference to the average itch or to the absolute worst itch (WI-NRS). 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. "Number analyzed" indicates number of participants with data available for analysis at a specified timepoint. | Mean | Standard Deviation | score on scale |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Percentage of Participants With ≥ 4- Point Decrease in 7-day Average Worst Itch - Numerical Rating Scale (WI-NRS) up to Week 14 | 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. | The mITT population included all randomized participants who received at least a single dose of IP. Overall number of participants analyzed indicates number of participants who were evaluable for this outcome measure. | Posted | Number | percentage of participants | Baseline up to Week 14 |
|
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Change From Baseline in Itch-related Quality of Life (ItchyQoL) Total Score at Week 14 | The ItchyQoL consists of 22 pruritus-specific items measuring how pruritus affects participant's QoL in the area of symptoms related to the itch condition (6 questions), functional limitations (7 questions), and emotions (9 questions). The participant scored each question never = 1, rarely = 2, sometimes = 3, often = 4, all the time = 5. The ItchyQoL total score were obtained as the sum of the 22 items ranging from 22 to 110, with higher score indicating worsening of pruritus. A negative change from baseline indicated improvement in the pruritus-related difficulties. | The mITT population included all randomized participants who received at least a single dose of IP. Overall number of participants analyzed indicates number of participants who were evaluable for this outcome measure. | Posted | Mean | Standard Deviation | score on a scale | Baseline, Week 14 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Change From Baseline in Prurigo Activity Score (PAS) Assessed by the Percentage of Participants With 1-Category Improvement in the Percentage of Pruriginous Lesions With Excoriations/Crusts (Item 5a) at Week 14 | PAS consists of 5 quantitative/qualitative measurements related to examination of skin: Type; number;distribution;quantitative number of lesions in a body part;activity. Prurigo lesion activity is recorded as a stage (0 to 4), based on percentage of overall lesions with relevant characteristic. Three types of PAS responders defined one for each of the following items: Pruriginous lesions with excoriations/crusts (item 5a);Healed lesions (item 5b);Number of lesions (item 2). Pruriginous lesions with excoriations/crusts (item 5a) was recorded from 0 to 4;where 0 = 0-25%1 = 26-50%,2 = 51-75%,3 = 76-90%,4 = 91-100%. Higher score=a greater number of pruriginous lesions with excoriations/crusts. A responder was defined as a participant who has at least 1-category improvement in the relevant item from baseline to Week 14. Baseline is defined as the last non-missing evaluation (including repeated and unscheduled assessments) taken prior to or on the date of first dose of study medication. | The mITT population included all randomized participants who received at least a single dose of IP. Overall number of participants analyzed indicates number of participants who were evaluable for this outcome measure. | Posted | Number | percentage of participants | Baseline, Week 14 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Change From Baseline in Patient-Reported Outcomes Measurement Information System (PROMIS) Sleep Disturbance Short Form 8a at Week 14 | PROMIS Sleep Disturbance Short Form 8a questionnaire is a tool for assessing sleep. It has 8 questions which measures sleep in the past 7 days.There is 1 broad sleep quality question with options:"very poor","poor","fair","good",and "very good".Remaining 7 questions are answered with:"not at all","a little bit","somewhat","quite a bit",and "very much".Lowest possible raw score=8; highest possible raw score=40. The T-score rescales raw score into a standardized score with a mean of 50 and an standard deviation of 10 derived from general population.Lowest possible T-score=28.9;highest possible T-score=76.6.Higher T-score shows more of the concept measured,higher the T-Score worse the sleep disturbance.Scores <55=normal limits, 55-60=mild, 61-70=moderate,and >70=severe sleep disturbance.Baseline=last non-missing evaluation (including repeated and unscheduled assessments) taken prior to or on the date of first dose of study medication.Negative change from baseline indicated better sleep. | The mITT population included all randomized participants who received at least a single dose of IP. Overall number of participants analyzed indicates number of participants who were evaluable for this outcome measure. | Posted | Mean | Standard Deviation | T-score | Baseline, Week 14 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Change From Baseline in 7-Day Average WI-NRS to Week 14 | The NRS is a 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. Baseline WI-NRS value was calculated as the arithmetic mean of the WI-NRS values (minimum of 5 required) taken for eligibility review by site at the time of randomization. A negative change from baseline indicates improvement in symptoms. | The mITT population included all randomized participants who received at least a single dose of IP. Overall number of participants analyzed indicates number of participants who were evaluable for this outcome measure. | Posted | Mean | Standard Deviation | score on a scale | Baseline, Week 14 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Change From Baseline in PAS Assessed by the Percentage of Participants With 1-Category Improvement in the Percentage of Healed Lesions (Item 5b) at Week 14 | PAS consists of 5 quantitative/qualitative measurements related to skin-Type; number; distribution; quantitative number of lesions in body part; activity. Prurigo lesion activity is recorded as stage (0 to 4), based on percentage of overall lesions with relevant characteristic. Three types of PAS responders are defined: Pruriginous lesions with excoriations/crusts (item 5a); Healed lesions (item 5b); Number of lesions (item 2). Prurigo lesions (item 5b), where 0 = 100%,1 = 75-99%,2 = 50-74%,3 = 25-49%,4 = 0-24% healed pruriginous lesions. Lower score=more number of healed pruriginous lesions. A responder was defined as a participant who has at least 1-category improvement in the relevant item from baseline to Week 14. Baseline was defined as the last non-missing evaluation (including repeated and unscheduled assessments) taken prior to or on the date of first dose of treatment. A negative change from baseline would indicate higher number of healed lesions. | The mITT population included all randomized participants who received at least a single dose of IP. | Posted | Number | percentage of participants | Baseline, Week 14 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Change From Baseline in PAS Assessed by the Percentage of Participants With 1-Category Improvement in the Percentage of Lesions (Item 2) at Week 14 | PAS consists of 5 quantitative/qualitative measurements of skin- Type; number; distribution; quantitative number of lesions in body part; activity. Prurigo lesion activity is recorded as stage (0 to 4) based on percentage of overall lesions with relevant characteristic. Three types of PAS responders are defined: Pruriginous lesions with excoriations/crusts (item 5a); Healed lesions (item 5b); Number of lesions (item 2). Prurigo lesion activity is recorded as a stage (0 to 4), based on the percentage of overall lesions with the relevant characteristic. A lower score indicates less number of pruriginous lesions. A responder was defined as a participant who has at least 1-category improvement in the relevant item from baseline to Week 14. Baseline was defined as the last non-missing evaluation (including repeated and unscheduled assessments) taken prior to or on the date of first dose of study medication. A negative change from baseline would indicate lower number of lesions. | The mITT population included all randomized participants who received at least a single dose of IP. | Posted | Number | percentage of participants | Baseline, Week 14 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Change From Baseline in Investigator Global Assessment-Prurigo Nodularis (IGA-PN) Assessed by the Percentage of Participants With 1-Category Improvement in Activity at Week 14 | The IGA-PN collects an investigator global assessment of status of PN skin lesions. The IGA-PN uses a 5-category scale (scoring 0 to 4) to describe the status of 2 aspects of disease: The Activity (amount of excoriation and crusting associated with the prurigo lesions), and the Stage (the quantitative presence and proportion of flattening of the lesions). The excoriation/crusting activity on the surface (PN-Activity) where it considers number of PN lesion with excoriations and crusts on the top, 0=clear (No nodules), 1 =small number, 2=minority of nodules, 3=most nodules, 4=severe (vast majority of nodules). A higher number indicates severe status of PN skin lesions. An IGA-PN responder for activity was defined as participants who has at a least 1-category improvement in the respective score from baseline to Week 14. Baseline was defined as the last non-missing evaluation (including repeated and unscheduled assessments) taken prior to or on the date of first dose of study medication. | The mITT population included all randomized participants who received at least a single dose of IP. Overall number of participants analyzed indicates number of participants who were evaluable for this outcome measure. | Posted | Number | percentage of participants | Baseline, Week 14 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Change From Baseline in IGA-PN Assessed by the Percentage of Participants With 1-Category Improvement in Stage at Week 14 | The IGA-PN collects an investigator global assessment of status of PN skin lesions. The IGA-PN uses a 5-category scale(scoring 0 to 4) to describe 2 aspects of disease. The Activity(amount of excoriation and crusting of prurigo lesions) and the Stage(the quantitative presence and proportion of flattening of lesions),where 0=clear(No nodules),1=Rare, flattened lesions, with no more than single dome-shaped palpable nodules(1-5 nodules), 2=Few,mostly flattened lesions, with small number of dome-shaped palpable nodules(6-19 nodules,3=Many lesions, partially flattened and dome-shaped palpable nodules (20-100 nodules),4=Abundant lesions, majority are dome-shaped palpable nodules (over 100 nodules).Higher number= presence of abundant lesions.Responder as defined as participants who has at a least 1-category improvement from baseline to Week 14.Baseline was defined as the last non-missing evaluation(repeated and unscheduled assessments)taken prior to or on the date of first dose of treatment. | The mITT population included all randomized participants who received at least a single dose of IP. Overall number of participants analyzed indicates number of participants who were evaluable for this outcome measure. | Posted | Number | percentage of participants | Baseline, Week 14 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Percentage of Participants Having a Patient Benefit Index, Pruritus Version (PBI-P) Score of ≥1 at Week 14 | PBI-P is an instrument that measures participant-defined treatment objectives and benefits acquired during the course of treatment.During and after therapy, the participant completes a matched "on-treatment" Treatment Benefits questionnaire and rates the extent to which the treatment objectives have been achieved.It consists of 27 multiple choice questions that can be answered "not at all","somewhat","moderately","quite","very".PBI-P global score is computed according to the score obtained for patient needs questionnaire (PNQ) and patient benefit questionnaire (PBQ).Score may only be computed if the participant has provided valid data on importance (PNQ) and benefit (PBQ) for at least 75% of the respective treatment goals,i.e., for at least 21 of the 27 items. Total score ranges from 0-135. Higher scores=more benefit received from the study to the participant.Responses "does/did not apply","question answered" are considered valid values when counting number of non-missing responses. | The mITT population included all randomized participants who received at least a single dose of IP. Overall number of participants analyzed indicates number of participants who were evaluable for this outcome measure. | Posted | Number | percentage of participants | At Week 14 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinued From Study Drug Due to TEAEs in DB Period | An AE is any untoward medical occurrence in a participant who administered a pharmaceutical product, and which does not necessarily have to have a causal relationship with the study drug. 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 serious adverse event (SAE) is any untoward medical occurrence that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. DB period TEAEs are defined as AEs that either start or worsen in severity on or after the first DB dose and prior to the first extension titration dose of study medication in the OLE period. TEAEs included both serious & non-serious TEAEs. | The safety population included all randomized participants who received at least a single dose of IP. | Posted | Count of Participants | Participants | Baseline up to Week 14 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Number of Participants Who Experienced TEAEs, Serious TEAEs, and Discontinued From Study Drug Due to TEAEs in OLE Period | An AE is 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 study drug. 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 serious adverse event (SAE) was any untoward medical occurrence that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. OLE period TEAEs are defined as AEs that either start or worsen in severity on or after the first extension titration dose of study medication. TEAEs included both serious & non-serious TEAEs. | The safety population included all randomized participants who received at least a single dose of IP. Overall number of participants analyzed indicates number of participants who entered OLE period. | Posted | Count of Participants | Participants | From Week 14 up to Week 56 |
|
DB Period: Baseline up to Week 14; OLE Period: From Week 14 to Week 56
The safety population included all randomized participants who received at least a single dose of IP.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | NAL ER (DB Period) | During the DB period, participants were titrated over 2 weeks to NAL ER 162 mg, orally, BID, followed by 162 mg, orally, BID, for 12 weeks. | 0 | 168 | 9 | 168 | 112 | 168 |
| EG001 | Placebo (DB Period) | 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. | 0 | 176 | 8 | 176 | 58 | 176 |
| EG002 | Prior NAL ER (OLE Period) | During the 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. | 0 | 107 | 7 | 107 | 49 | 107 |
| EG003 | Prior Placebo (OLE Period) | 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). | 0 | 144 | 7 | 144 | 95 | 144 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cellulitis | Infections and infestations | MedDRA 21.0 | Systematic Assessment |
| |
| Erysipelas | Infections and infestations | MedDRA 21.0 | Systematic Assessment |
| |
| Postoperative wound infection | Infections and infestations | MedDRA 21.0 | Systematic Assessment |
| |
| Pyelonephritis | Infections and infestations | MedDRA 21.0 | Systematic Assessment |
| |
| Neurodermatitis | Skin and subcutaneous tissue disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Dermatitis | Skin and subcutaneous tissue disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Osteonecrosis | Musculoskeletal and connective tissue disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Sacroiliitis | Musculoskeletal and connective tissue disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Angina unstable | Cardiac disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Hypertensive heart disease | Cardiac disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Angle closure glaucoma | Eye disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Vision blurred | Eye disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Ankle fracture | Injury, poisoning and procedural complications | MedDRA 21.0 | Systematic Assessment |
| |
| Ligament rupture | Injury, poisoning and procedural complications | MedDRA 21.0 | Systematic Assessment |
| |
| Ligament sprain | Injury, poisoning and procedural complications | MedDRA 21.0 | Systematic Assessment |
| |
| Overdose | Injury, poisoning and procedural complications | MedDRA 21.0 | Systematic Assessment |
| |
| Spinal compression fracture | Injury, poisoning and procedural complications | MedDRA 21.0 | Systematic Assessment |
| |
| Spinal fracture | Injury, poisoning and procedural complications | MedDRA 21.0 | Systematic Assessment |
| |
| Diabetes mellitus | Metabolism and nutrition disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Serous cystadenocarcinoma ovary | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 21.0 | Systematic Assessment |
| |
| Clear cell renal cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 21.0 | Systematic Assessment |
| |
| Cerebrovascular accident | Nervous system disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Dysarthria | Nervous system disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Migraine with aura | Nervous system disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Ureterolithiasis | Renal and urinary disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Nephrolithiasis | Renal and urinary disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Chronic obstructive pulmonary disease | Respiratory, thoracic and mediastinal disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Interstitial lung disease | Respiratory, thoracic and mediastinal disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Vertigo | Ear and labyrinth disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Cholelithiasis | Hepatobiliary disorders | MedDRA 21.0 | Systematic Assessment |
| |
| SARS-CoV-2 test positive | Investigations | MedDRA 21.0 | Systematic Assessment |
| |
| Confusional state | Psychiatric disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Disorientation | Psychiatric disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Dissociation | Psychiatric disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Empyema | Infections and infestations | MedDRA 21.0 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Somnolence | Nervous system disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Treatment noncompliance | General disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Medication error | Injury, poisoning and procedural complications | MedDRA 21.0 | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 21.0 | Systematic Assessment |
|
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Chief Development Officer | Trevi Therapeutics, Inc. | 203-304-2499 | info@trevitherapeutics.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jun 1, 2022 | Apr 23, 2025 | SAP_001.pdf |
Not provided
|
|
|
|
|
|
|
| OG001 | Placebo | 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). |
|
|
|
| OG001 | Placebo | 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). |
|
|
|
|
|
| OG001 |
| Placebo |
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). |
|
|
| OG001 |
| Placebo |
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). |
|
|
| OG001 | Placebo | 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). |
|
|
| OG001 | Placebo | 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). |
|
|
| OG001 | Placebo | 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). |
|
|
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. |
|
|
| Prior Placebo (OLE Period) |
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). |
|
|