Trial Outcomes & Findings for PRISM Study-Pruritus Relief Through Itch Scratch Modulation (NCT NCT03497975)

Last Updated: 2025-06-24

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2/PHASE3

Target enrollment

353 participants

Primary outcome timeframe

Baseline up to Week 14

Results posted on

2025-06-24

Participant Flow

Participants were enrolled at 70 sites in Germany, Poland, Austria, France and the United States from 07 August 2018 to 24 February 2023.

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.

Participant milestones

Participant milestones
Measure	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.	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).
Overall Study STARTED	173	180
Overall Study Modified Intent-to-treat (mITT) Analysis Set	168	176
Overall Study Participants Who Entered the OLE Period	107	144
Overall Study COMPLETED	71	80
Overall Study NOT COMPLETED	102	100

Reasons for withdrawal

Reasons for withdrawal
Measure	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.	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).
Overall Study Withdrew Consent	34	35
Overall Study Lost to Follow-up	7	7
Overall Study Physician Decision	4	5
Overall Study Discontinued	42	39
Overall Study Reason Not Specified	15	14

Baseline Characteristics

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.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	NAL ER n=168 Participants 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.	Placebo n=176 Participants 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).	Total n=344 Participants Total of all reporting groups
Age, Continuous	59.6 years STANDARD_DEVIATION 13.25 • n=168 Participants	55.9 years STANDARD_DEVIATION 14.32 • n=176 Participants	57.7 years STANDARD_DEVIATION 13.91 • n=344 Participants
Sex: Female, Male Female	100 Participants n=168 Participants	112 Participants n=176 Participants	212 Participants n=344 Participants
Sex: Female, Male Male	68 Participants n=168 Participants	64 Participants n=176 Participants	132 Participants n=344 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	6 Participants n=168 Participants	7 Participants n=176 Participants	13 Participants n=344 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	63 Participants n=168 Participants	66 Participants n=176 Participants	129 Participants n=344 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	99 Participants n=168 Participants	103 Participants n=176 Participants	202 Participants n=344 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=168 Participants	0 Participants n=176 Participants	0 Participants n=344 Participants
Race (NIH/OMB) Asian	6 Participants n=168 Participants	7 Participants n=176 Participants	13 Participants n=344 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	6 Participants n=168 Participants	11 Participants n=176 Participants	17 Participants n=344 Participants
Race (NIH/OMB) Black or African American	24 Participants n=168 Participants	23 Participants n=176 Participants	47 Participants n=344 Participants
Race (NIH/OMB) White	132 Participants n=168 Participants	134 Participants n=176 Participants	266 Participants n=344 Participants
Race (NIH/OMB) More than one race	0 Participants n=168 Participants	1 Participants n=176 Participants	1 Participants n=344 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=168 Participants	0 Participants n=176 Participants	0 Participants n=344 Participants
Worst Itch - Numerical Rating Scale (WI-NRS) Score	8.637 score on scale STANDARD_DEVIATION 0.9115 • n=167 Participants • 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.	8.650 score on scale STANDARD_DEVIATION 0.8902 • n=176 Participants • 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.	8.643 score on scale STANDARD_DEVIATION 0.8993 • n=343 Participants • 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.

PRIMARY outcome

Timeframe: Baseline up to Week 14

Population: 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.

Outcome measures

Outcome measures
Measure	NAL ER n=99 Participants 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.	Placebo n=131 Participants 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).
Percentage of Participants With ≥ 4- Point Decrease in 7-day Average Worst Itch - Numerical Rating Scale (WI-NRS) up to Week 14	24.24 percentage of participants	14.50 percentage of participants

SECONDARY outcome

Timeframe: Baseline, 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.

Outcome measures

Outcome measures
Measure	NAL ER n=95 Participants 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.	Placebo n=127 Participants 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).
Change From Baseline in Itch-related Quality of Life (ItchyQoL) Total Score at Week 14	-17.4 score on a scale Standard Deviation 18.01	-8.8 score on a scale Standard Deviation 17.15

SECONDARY outcome

Timeframe: Baseline, 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.

Outcome measures

Outcome measures
Measure	NAL ER n=112 Participants 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.	Placebo n=146 Participants 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).
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	54.5 percentage of participants	41.1 percentage of participants

SECONDARY outcome

Timeframe: Baseline, 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.

Outcome measures

Outcome measures
Measure	NAL ER n=96 Participants 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.	Placebo n=127 Participants 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).
Change From Baseline in Patient-Reported Outcomes Measurement Information System (PROMIS) Sleep Disturbance Short Form 8a at Week 14	-9.5 T-score Standard Deviation 10.01	-4.5 T-score Standard Deviation 8.44

SECONDARY outcome

Timeframe: Baseline, 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.

Outcome measures

Outcome measures
Measure	NAL ER n=99 Participants 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.	Placebo n=131 Participants 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).
Change From Baseline in 7-Day Average WI-NRS to Week 14	-2.5 score on a scale Standard Deviation 2.36	-1.6 score on a scale Standard Deviation 2.14

SECONDARY outcome

Timeframe: Baseline, Week 14

Population: The mITT population included all randomized participants who received at least a single dose of IP.

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.

Outcome measures

Outcome measures
Measure	NAL ER n=168 Participants 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.	Placebo n=176 Participants 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).
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	39.3 percentage of participants	34.7 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Week 14

Population: The mITT population included all randomized participants who received at least a single dose of IP.

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.

Outcome measures

Outcome measures
Measure	NAL ER n=168 Participants 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.	Placebo n=176 Participants 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).
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	25.0 percentage of participants	18.8 percentage of participants

SECONDARY outcome

Timeframe: Baseline, 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.

Outcome measures

Outcome measures
Measure	NAL ER n=112 Participants 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.	Placebo n=146 Participants 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).
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	57.1 percentage of participants	41.1 percentage of participants

SECONDARY outcome

Timeframe: Baseline, 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.

Outcome measures

Outcome measures
Measure	NAL ER n=112 Participants 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.	Placebo n=146 Participants 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).
Change From Baseline in IGA-PN Assessed by the Percentage of Participants With 1-Category Improvement in Stage at Week 14	43.8 percentage of participants	32.9 percentage of participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	NAL ER n=87 Participants 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.	Placebo n=95 Participants 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).
Percentage of Participants Having a Patient Benefit Index, Pruritus Version (PBI-P) Score of ≥1 at Week 14	100.0 percentage of participants	100.0 percentage of participants

SECONDARY outcome

Timeframe: Baseline up to Week 14

Population: The safety population included all randomized participants who received at least a single dose of IP.

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.

Outcome measures

Outcome measures
Measure	NAL ER n=168 Participants 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.	Placebo n=176 Participants 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).
Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinued From Study Drug Due to TEAEs in DB Period Participants with TEAEs	136 Participants	106 Participants
Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinued From Study Drug Due to TEAEs in DB Period Participants with Serious TEAEs	9 Participants	8 Participants
Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinued From Study Drug Due to TEAEs in DB Period Participants with Study Drug Discontinuation Due to TEAEs	53 Participants	13 Participants

SECONDARY outcome

Timeframe: From Week 14 up to Week 56

Population: 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.

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.

Outcome measures

Outcome measures
Measure	NAL ER n=107 Participants 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.	Placebo n=144 Participants 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).
Number of Participants Who Experienced TEAEs, Serious TEAEs, and Discontinued From Study Drug Due to TEAEs in OLE Period Participants with TEAEs	84 Participants	116 Participants
Number of Participants Who Experienced TEAEs, Serious TEAEs, and Discontinued From Study Drug Due to TEAEs in OLE Period Participants with Serious TEAEs	7 Participants	7 Participants
Number of Participants Who Experienced TEAEs, Serious TEAEs, and Discontinued From Study Drug Due to TEAEs in OLE Period Participants with Study Drug Discontinuation Due to TEAEs	8 Participants	30 Participants

Adverse Events

NAL ER (DB Period)

Serious events: 9 serious events

Other events: 112 other events

Deaths: 0 deaths

Placebo (DB Period)

Serious events: 8 serious events

Other events: 58 other events

Deaths: 0 deaths

Prior NAL ER (OLE Period)

Serious events: 7 serious events

Other events: 49 other events

Deaths: 0 deaths

Prior Placebo (OLE Period)

Serious events: 7 serious events

Other events: 95 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	NAL ER (DB Period) n=168 participants at risk 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.	Placebo (DB Period) n=176 participants at risk 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 NAL ER (OLE Period) n=107 participants at risk 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.	Prior Placebo (OLE Period) n=144 participants at risk 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).
Gastrointestinal disorders Nausea	31.0% 52/168 • 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.	9.1% 16/176 • 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.	12.1% 13/107 • 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.	30.6% 44/144 • 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.
Gastrointestinal disorders Constipation	15.5% 26/168 • 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.	4.0% 7/176 • 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.	3.7% 4/107 • 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.	7.6% 11/144 • 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.
Gastrointestinal disorders Vomiting	11.3% 19/168 • 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.	3.4% 6/176 • 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.	2.8% 3/107 • 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.	13.9% 20/144 • 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.
Nervous system disorders Dizziness	31.5% 53/168 • 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.	3.4% 6/176 • 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.	4.7% 5/107 • 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.	20.8% 30/144 • 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.
Nervous system disorders Headache	15.5% 26/168 • 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.	8.0% 14/176 • 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.	7.5% 8/107 • 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.	15.3% 22/144 • 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.
Nervous system disorders Somnolence	14.9% 25/168 • 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.	3.4% 6/176 • 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.	2.8% 3/107 • 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.	13.2% 19/144 • 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.
General disorders Fatigue	13.7% 23/168 • 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.	5.7% 10/176 • 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.	4.7% 5/107 • 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.	12.5% 18/144 • 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.
Skin and subcutaneous tissue disorders Pruritus	5.4% 9/168 • 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.	5.1% 9/176 • 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.	4.7% 5/107 • 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.	4.2% 6/144 • 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.
Skin and subcutaneous tissue disorders Hyperhidrosis	5.4% 9/168 • 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.	0.00% 0/176 • 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.	2.8% 3/107 • 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.	3.5% 5/144 • 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.
Gastrointestinal disorders Diarrhoea	4.2% 7/168 • 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.	2.8% 5/176 • 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.	9.3% 10/107 • 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.	10.4% 15/144 • 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.
General disorders Treatment noncompliance	2.4% 4/168 • 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.	1.7% 3/176 • 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.	7.5% 8/107 • 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.	5.6% 8/144 • 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.
Injury, poisoning and procedural complications Medication error	2.4% 4/168 • 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.	3.4% 6/176 • 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.	10.3% 11/107 • 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.	9.7% 14/144 • 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.
Musculoskeletal and connective tissue disorders Arthralgia	2.4% 4/168 • 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.	1.1% 2/176 • 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.	5.6% 6/107 • 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.	2.1% 3/144 • 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.

Additional Information

Chief Development Officer

Trevi Therapeutics, Inc.

Phone: 203-304-2499

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place